acid-phosphatase and Gaucher-Disease

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly-described chemokine, pulmonary and activation-regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin-converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.. For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.

Topics: Acid Phosphatase; Biomarkers; Chemokines, CC; Gaucher Disease; Hexosaminidases; Humans; Platelet Count; Spleen

Acid phosphatases (APs) are a family of enzymes that are widespread in nature, and can be found in many animal and plant species. Mystery surrounds the precise functional role of these molecular facilitators, despite much research. Yet, paradoxically, human APs have had considerable impact as tools of clinical investigation and intervention. One particular example is tartrate resistant acid phosphatase, which is detected in the serum in raised amounts accompanying pathological bone resorption. This article seeks to explore the identity and diversity of APs, and to demonstrate the relation between APs, human disease, and clinical diagnosis.

Topics: Acid Phosphatase; alpha-Macroglobulins; Biomarkers; Bone Resorption; Favism; Gaucher Disease; Humans; Intracellular Fluid; Isoenzymes; Leukemia, Hairy Cell; Male; Osteoclasts; Osteoporosis; Prostate; Prostatic Neoplasms; Protein Binding; Reactive Oxygen Species; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Antigens; Blood Protein Disorders; Gaucher Disease; Glucosylceramidase; Glucosylceramides; Humans; Hypergammaglobulinemia; Multiple Myeloma

Increased acid phosphatase activity in the serum and tissues of patients with Gaucher's disease has now been recognized for two decades, but as yet no relation has been established between the enzyme and the etiology and progress of the disease. Here, we review results obtained by various investigators, ranging from a consideration of the methods used for the evaluation of serum acid phosphatase in Gaucher's disease to the most recent findings regarding the purification and characterization of two acid phosphatase isoenzymes from the spleen from patients with Gaucher's disease. We also discuss the intracellular location of tissue acid phosphatase in patients with Gaucher's disease and its contribution to the increased activity in serum.

Topics: Acid Phosphatase; Gaucher Disease; Humans; Isoenzymes; Kinetics; Spectrometry, Fluorescence; Spleen; Splenectomy; Substrate Specificity

Topics: Acid Phosphatase; Adult; Aged; Diethylstilbestrol; Estradiol; Female; Gaucher Disease; Humans; Isoenzymes; Male; Methods; Middle Aged; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Bone Diseases; Cerebrosides; Epilepsy, Temporal Lobe; Gaucher Disease; Graft Rejection; Graft vs Host Reaction; Humans; Intellectual Disability; Kyphosis; Lymphopenia; Male; Postoperative Complications; Radionuclide Imaging; Spleen; Technetium; Thrombocytopenia; Transplantation, Homologous

Topics: Acid Phosphatase; Acid-Base Equilibrium; Chediak-Higashi Syndrome; Cytoplasm; Diffuse Cerebral Sclerosis of Schilder; Gaucher Disease; Genes, Recessive; Glycogen Storage Disease; Humans; Hydrolases; Lipidoses; Lysosomes; Metabolism, Inborn Errors; Niemann-Pick Diseases

Topics: Acid Phosphatase; Adolescent; Adult; Age Factors; Brain; Cerebrosides; Child; Child, Preschool; Clinical Enzyme Tests; Diffuse Cerebral Sclerosis of Schilder; Female; Gaucher Disease; Glycoside Hydrolases; Humans; Infant; Leukocytes; Liver; Male; Niemann-Pick Diseases; Phospholipases; Sphingomyelins; Spleen; Sulfatases; Veins

The aim of the study was to evaluate the efficiency of the biomarkers chitotriosidase (Chito), total acid phosphatase (TACP), angiotensin converting enzyme (ACE) and ferritin in the diagnosis of Gaucher disease (GD) and to assess the utility of biomarkers for monitoring the effects of enzyme replacement therapy (ERT).. Forty treatment-naive Gaucher patients were studied. 27/40 GP were put on ERT and monitored every 6 months.. The baseline median values of Chito, TACP, ACE and ferritin were highly elevated in GP: 10216 nmol/mL/h, 26.1 U/L, 253 U/L, 515 μg/L, and 555 μg/L, respectively. The only significant difference between mild and moderate GP subgroups is observed for Chito activity (p=0.0116). During ERT, Chito showed the steepest decrease in regard to TACP and ACE, mainly within the first year (71.4%).. Among these biomarkers, Chito proved to be the most useful biomarker for diagnosing GD and monitoring the ERT.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Child; Enzyme Replacement Therapy; Female; Ferritins; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Serbia; Severity of Illness Index; Young Adult

Gaucher's disease, the most prevalent of the sphingolipid storage disorders, is caused by a deficiency of the enzyme glucocerebrosidase (glucosylceramidase). Enzyme replacement was proposed as a therapeutic strategy for this disorder in 1966. To assess the clinical effectiveness of this approach, we infused macrophage-targeted human placental glucocerebrosidase (60 IU per kilogram of body weight every 2 weeks for 9 to 12 months) into 12 patients with type 1 Gaucher's disease who had intact spleens. The frequency of infusions was increased to once a week in two patients (children) during part of the trial because they had clinically aggressive disease.. The hemoglobin concentration increased in all 12 patients, and the platelet count in 7. Serum acid phosphatase activity decreased in 10 patients during the trial, and the plasma glucocerebroside level in 9. Splenic volume decreased in all patients after six months of treatment, and hepatic volume in five. Early signs of skeletal improvements were seen in three patients. The enzyme infusions were well tolerated, and no antibody to the exogenous enzyme developed.. Intravenous administration of macrophage-targeted glucocerebrosidase produces objective clinical improvement in patients with type 1 Gaucher's disease. The hematologic and visceral responses to enzyme replacement develop more rapidly than the skeletal response.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Development; Child; Female; Gaucher Disease; Glucosylceramidase; Glucosylceramides; Hemoglobins; Humans; Macrophages; Male; Organ Size; Spleen

Topics: Acid Phosphatase; Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Female; Galactosidases; Gaucher Disease; Glucuronidase; Glycoside Hydrolases; Humans; Infant; Lysosomes; Male

Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

Topics: Acid Phosphatase; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone and Bones; Bone Diseases; Gaucher Disease; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Peptide Fragments; Procollagen; Tartrate-Resistant Acid Phosphatase

Gaucher disease type 1 (GD1) was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed. We describe the management of eight GD1 patients in Slovenia who were diagnosed between the ages of 2 and 15 years.. Patients were individually assessed to establish initial enzyme doses and monitored frequently to determine the effects of long-term enzyme dose regimens. Outcomes up to 10 years after long-term treatment are described by changes in the Zimran severity score index, chitotriosidase and acid phosphatase levels, and after 2001, bone parameters (DEXA bone mineral density scores and the MRI bone marrow burden score).. Following the initiation of enzyme therapy with individualized dose regimens (range 25-56 U/kg/14 days) and followed by a gradual reduction of doses (range 12-35 U/kg/14 days) during long-term maintenance, disease status improved in all patients as measured by the Zimran severity score index (from a mean of 11.25 [median 11.5] before therapy to a mean of 4.12 [median 3.5] at last report). Anemia and leucopenia resolved in all patients, chitotriosidase and acid phosphatase levels decreased in all patients (and by over 75% in six patients) within 1 year of treatment. Bone marrow burden scores improved in all monitored patients and DXA scores improved in six of seven monitored patients.. We conclude that enzyme therapy with relatively low, individualized dose regimens is well-tolerated and effective in children and young adults with GD1 disease, who are regularly monitored for changes in disease status.

Topics: Acid Phosphatase; Adolescent; Adult; Child; Child, Preschool; Dose-Response Relationship, Drug; Enzyme Replacement Therapy; Female; Follow-Up Studies; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Infant; Infusions, Intravenous; Male; Prevalence; Retrospective Studies; Slovenia; Time Factors; Treatment Outcome; Young Adult

Known biomarkers of Gaucher-disease activity are platelets, chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and ferritin. The aim of this study was to retrospectively evaluate the frequency of bone events (BE) and biomarker changes during two periods: diagnosis to first enzyme-replacement therapy (ERT) and the latter to the closing date.. BE of 62 treated patients, among the 73-patient cohort followed at Beaujon Hospital, Clichy, France, were described with Kaplan-Meier curves, and linear-mixed models were used to analyze their biomarker changes and the influence of several covariates (splenectomy, diagnosis year, genotype, age at diagnosis and sex).. BE occurred before (54 events in 21 patients), but also during, ERT (12 events in 10 patients), with respective frequencies (95% confidence interval) at 10 years of 22.4% (13.3 to 36.3) and 20.0% (10.2 to 36.9). Biomarker slope changes before and during ERT differed significantly for platelets (+190/mm3/year and 7,035/mm3/year, respectively; P < 0.0001) and ferritin (+4% and -14%; P < 0.0001). High ferritin levels and low platelet counts at ERT onset were significantly associated with BE during ERT (P = 0.019 and 0.039, respectively). Covariates significantly influenced biomarker changes (baseline and/or slope): splenectomy affected platelets (baseline and changes), TRAP changes and chitotriosidase changes; diagnosis date influenced ACE and TRAP baseline values; and genotype influenced chitotriosidase baseline and changes.. Platelet counts and ferritin levels and their slope changes at ERT onset seem to predict BE during treatment. Biomarker baseline values and changes are dependent on several covariables.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers; Bone Diseases; Child; Child, Preschool; Cohort Studies; Disease Progression; Enzyme Replacement Therapy; Female; Ferritins; Fractures, Bone; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Infant; Isoenzymes; Kaplan-Meier Estimate; Male; Middle Aged; Peptidyl-Dipeptidase A; Platelet Count; Predictive Value of Tests; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Young Adult

Niemann-Pick disease type C (NPC) is a model for inborn errors of metabolism whose gene product mediates molecular trafficking rather than catabolizing macromolecules, as in classic lipidoses. We report the case of an infant who presented with hepatosplenomegaly without neurological abnormalities. Decreased activity of acid β-glucosidase and elevated serum chitotriosidase and tartrate-resistant acid phosphatase on repeated measurements led to initial diagnosis of Gaucher disease (GD). Failure to respond to enzyme replacement therapy after one year, however, put the diagnosis in question. Cholesterol esterification assays in cultured skin fibroblasts and NPC gene analysis led to the correct diagnosis of NPC. The patient had markedly reduced cholesterol esterification and was a compound heterozygote for a known and a novel mutation in the NPC gene (395delC and 2068insTCCC), which are both predicted to lead to protein truncation. Although the full phenotype of NPC involves hepatosplenomegaly and neurodegenerative disease, the initial presentation in a pediatric patient may be restricted to visceral disease. Of interest, this patient had decreased activity of leukocyte acid β-glucosidase activity and elevated serum chitotriosidase to levels often seen in GD. Although acid β-glucosidase activity in leukocytes was low, it was in the normal range in skin fibroblasts. Therefore, diagnostic delay may occur in NPC due to false positive testing for GD. Diagnosis of NPC requires a high index of suspicion and should be considered in a patient with hepatosplenomegaly even in the absence of neurodevelopmental signs. Prompt diagnosis will become increasingly important as effective therapies are developed for NPC.

Topics: 1-Deoxynojirimycin; Acid Phosphatase; Biomarkers; Carrier Proteins; Cells, Cultured; Cholesterol Esters; Diagnostic Errors; DNA Mutational Analysis; Enzyme Inhibitors; Enzyme Replacement Therapy; Esterification; Female; Gaucher Disease; Genetic Predisposition to Disease; Glucosylceramidase; Glucosyltransferases; Hepatomegaly; Heterozygote; Hexosaminidases; Humans; Infant; Intracellular Signaling Peptides and Proteins; Isoenzymes; Membrane Glycoproteins; Mutation; Niemann-Pick C1 Protein; Niemann-Pick Disease, Type C; Phenotype; Predictive Value of Tests; Splenomegaly; Tartrate-Resistant Acid Phosphatase; Unnecessary Procedures

A 63-year-old man who was incidentally found to have thrombocytopenia at a periodic physical examination visited our hospital. The spleen was palpable 3 finger-breadths below the navel level, and the liver was palpable 1 finger-breadth below the right costal margin. Peripheral blood examination showed WBC 2,900/microl, Hb 13.4 g/dl, and platelets 54 X 10(3)/ microl. Gaucher cells were recognized in the bone marrow by aspiration, and serum levels of total acid phosphatase and angiotensin converting enzyme were increased. Glucocerebrosidase activity was lower than the control level in bone marrow stroma cells, and modification of glucocerebrosidase genotype N188S was shown, which had been identified in the past. Furthermore, neurological examination was normal. Based on these results, we diagnosed the patient with Gaucher disease type I, and started enzyme replacement therapy. Gaucher disease is rare in Japanese, approximately 100 cases having been reported; diagnosis at older age is also relatively rare and, as far as we know, the oldest age reported in Japanese was 57 years old. Gaucher disease should be considered a differential diagnosis when thrombocytopenia and splenomegaly are found in elderly patients, although it is relatively rare.

Topics: Acid Phosphatase; Age of Onset; Biomarkers; Bone Marrow Cells; Diagnosis, Differential; Gaucher Disease; Glucosylceramidase; Humans; Male; Middle Aged; Mutation; Peptidyl-Dipeptidase A; Splenomegaly; Thrombocytopenia

Several markers have been developed for the biochemical monitoring of Gaucher disease. Three of the most commonly used markers are acid phosphatase, angiotensin-converting enzyme (ACE) and chitotriosidase. The rationale for using all three concurrently is not clear. A retrospective study was therefore carried out on data collected from 28 paediatric patients treated with enzyme replacement therapy. All three markers fell with time. However, chitotriosidase showed the steepest time trend, the largest trend by case interaction, and the lowest residual variance, making it the most reliable of the three. ACE correlated strongly with chitotriosidase, but acid phosphatase did not correlate well with either and also had the largest residual variance, indicating that it was too 'noisy' to be informative. The absence of a 'gold standard' for assessing Gaucher disease complicates the interpretation of these findings, but they suggest that acid phosphatase be dropped from routine clinical practice, and that chitriosidase be used in preference to ACE.

Topics: Acid Phosphatase; Analysis of Variance; Biomarkers; Chemistry, Clinical; Child; Evaluation Studies as Topic; Fibroblasts; Gaucher Disease; Hexosaminidases; Humans; Peptidyl-Dipeptidase A; Reproducibility of Results; Retrospective Studies; Time Factors

The excessive storage of cellular debris in the lysosomal storage disorders triggers a variety of cellular responses. Some of these responses are maladaptative and result in the pathology of these diseases. To some extent, cellular responses are specific to the stored material, which influences the pathophysiology of the disease and results in some of its characteristic features.. A large body of data has been collected for three biochemical (surrogate) markers of Gaucher Disease: angiotensin converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and chitotriosidase (CHITO) using currently available enzyme analysis. Follow up data was gathered in a group of 18 patients.. The three markers are correlated between each other and are useful indicators of the disease progress and its response to enzyme replacement therapy (ERT). Retrospective analysis of clinical records and comparison of chitotriosidase values with the baseline Severity Score Index (SSI) allowed prediction of the response patterns for this marker when long-term ERT (>24 months) was evaluated.. The less severely affected patients are more likely to normalize their chitotriosidase activities after long term ERT.

Topics: Acid Phosphatase; Biomarkers; Disease Progression; Drug Monitoring; Enzyme Therapy; Enzymes; Follow-Up Studies; Gaucher Disease; Hexosaminidases; Humans; Isoenzymes; Peptidyl-Dipeptidase A; Retrospective Studies; Severity of Illness Index; Tartrate-Resistant Acid Phosphatase

This study investigated 51 patients with Type 1 Gaucher's disease clinically and radiographically for the presence of osteonecrosis. Twenty-five female and 26 male patients with a mean age of 37 years were evaluated retrospectively for osteonecrosis of the proximal and distal femur, proximal tibia, and proximal humerus. All patients were examined before enzyme replacement therapy. Gender, age at diagnosis, prior splenectomy, hematocrit, platelet count, acid phosphatase level, radiographs of the long bones, and magnetic resonance quantitative chemical shift imaging of the spine were analyzed to see if any of these values or findings were associated with the presence of osteonecrosis. Splenectomy was an independent risk factor for the presence of osteonecrosis in three of the four major sites and was a multivariate risk factor for osteonecrosis of the proximal femur and tibia. Male gender was the other significant multivariate risk factor for osteonecrosis of the humerus and distal femur when all sites were taken into account.

Topics: Acid Phosphatase; Adult; Age Factors; Confidence Intervals; Female; Femur; Femur Head Necrosis; Gaucher Disease; Hematocrit; Humans; Humerus; Lumbar Vertebrae; Magnetic Resonance Spectroscopy; Male; Multivariate Analysis; Odds Ratio; Osteonecrosis; Platelet Count; Radiography; Retrospective Studies; Risk Factors; Sex Factors; Splenectomy; Tibia

The major elements of bone pathology in Gaucher disease are a failure of osteoclast and osteoblast function, resulting in osteopenia and also osteonecrosis. T lymphocytes have recently been found to be involved in the regulation of osteoblast/osteoclast activity in vitro. In the present report the peripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients. A total of 31 patients were studied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized patients present a decrease in absolute numbers of peripheral blood T lymphocytes, specially the CD4+ T subset. However, when patients were analyzed with respect to the presence of bone disease, the number of CD8+ T lymphocytes was found to be statistically significantly lower in patients presenting bone involvement. Furthermore, lower numbers of CD8+ T lymphocytes were significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell activity. These in vivo findings are in agreement with the results reached in vitro by others. They provide an additional marker of disease severity in Gaucher disease. In the group of genotyped Gaucher disease patients, the majority of the N370S homozygous patients presented a clinically milder phenotype, including the absence of bone involvement, confirming earlier reports predicting that a number of these patients may remain undiagnosed. Collectively the homozygosity for the N370S mutation and normal T cell numbers may provide additional markers for the clinical heterogeneity of Gaucher disease.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Female; Gaucher Disease; Genotype; Glucosylceramidase; Humans; Isoenzymes; Lymphocyte Count; Male; Middle Aged; Recombinant Proteins; Splenectomy; T-Lymphocytes; Tartrate-Resistant Acid Phosphatase

The demonstration of tartrate-resistant acid phosphatase (TRAP) activity has long been a cornerstone in the diagnosis of hairy cell leukemia (HCL). Recently a monoclonal antibody to this enzyme has been developed that can be used in an immunoperoxidase method on paraffin-embedded tissues. By using a peroxidase-labeled streptavidin biotin method, paraffin sections of B5 and formalin-fixed tissue from 86 cases of HCL (41 bone marrow, 36 spleen, 9 liver) were stained with the antibody to TRAP and compared against staining for CD20 (L26) and DBA.44 (DAKO, Carpinteria, Calif). In addition, 193 specimens (127 bone marrow, 42 lymph node, 19 spleen, 5 other) from a variety of neoplastic and nonneoplastic hematologic conditions were stained using the monoclonal antibody to TRAP. For comparison, these cases were also stained with DBA.44. In the cases of HCL, 80 of 86 specimens were immunoreactive for TRAP. While the antibody to TRAP generally stained less than 50% of the hairy cells, CD20 and DBA.44 stained 90% and 50% to 60% of hairy cells, respectively. Two of three cases of marginal zone lymphoma showed weak immunoreactivity to the TRAP antibody. Two specimens from a patient with Gaucher's disease and 8 of 13 cases of mastocytosis also showed positivity to the TRAP antibody in the macrophages and mast cells, respectively. In contrast, staining for DBA.44 was positive in 3 of 9 cases of B-cell large cell lymphoma, 1 of 4 cases of mantle cell lymphoma, and in the paraimmunoblasts of 1 of 7 cases of small lymphocytic lymphoma. Only HCL was TRAP and DBA.44 positive. This antibody to TRAP is a useful addition to the diagnosis of HCL but should be used in conjunction with CD20 and DBA.44. The use of this antibody to determine minimal residual disease after chemotherapy was not addressed.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow; Bone Marrow Neoplasms; Diagnosis, Differential; Gaucher Disease; Humans; Immunohistochemistry; Isoenzymes; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Liver; Liver Neoplasms; Lymph Nodes; Lymphoma, B-Cell; Lymphoproliferative Disorders; Macrophages; Mast Cells; Paraffin Embedding; Pathology, Clinical; Spleen; Splenic Neoplasms; Tartrate-Resistant Acid Phosphatase

Methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase activity was increased 53- to 484-fold in plasma from Gaucher disease patients and no activator could be found. High activity was also measured in other lysosomal storage diseases including Krabbe disease, Wolman disease, GM1-gangliosidosis and to a lesser extent Niemann-Pick disease type B, but the activities were lower than the lowest values in Gaucher patients. Kinetic properties of the high activity in Gaucher plasma were similar to those of controls. It is not known whether the increased activity represents intrinsic enzyme activity or increased enzyme concentration. It is possible that this enzyme may help in the detection of Gaucher disease or in the assessment of enzyme therapy with beta-D-glucosidase (Ceredase).

Topics: Acid Phosphatase; Chitinases; Gaucher Disease; Humans

Topics: Acid Phosphatase; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Lysosomes; Macrophages

Topics: Acid Phosphatase; Anemia; Child, Preschool; Electroencephalography; Female; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Injections, Intravenous

We have characterized four monoclonal antibodies (mAbs) to the purple ("tartrate-resistant," band 5) acid phosphatase of the human osteoclast (TRAP) and used these to develop a specific serum immunoassay. All four mAbs are of high affinity (Ka = 1-5 x 10(8) L/mol) with a very fast Kassoc (0.2-2.0 x 10(5) L mol-1 s-1) and a moderate Kdissoc (1-3 x 10(-3) s). Two of the mAbs were selected to develop a time-resolved fluorescence immunoassay to measure serum concentrations of TRAP. The mean serum immunoreactive TRAP in a group of healthy premenopausal women and men was 3.7 +/- 1.8 micrograms/L (mean +/- SD) and 3.5 +/- 1.6 micrograms/L, respectively. Significantly higher concentrations of TRAP were found in postmenopausal women (6.3 +/- 2.3 micrograms/L) and in eight patients with Gaucher disease (19.3 +/- 4.7 micrograms/L). Further studies are required to investigate the value of serum TRAP as a marker of bone resorption.

Topics: Acid Phosphatase; Adolescent; Adult; Antibodies, Monoclonal; Antibody Affinity; Biomarkers; Bone Diseases; Bone Resorption; Female; Fluoroimmunoassay; Gaucher Disease; Humans; Isoenzymes; Male; Middle Aged; Postmenopause; Premenopause; Recombinant Proteins; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Acid phosphatases in brain and cultured lymphoblasts from patients affected with neuronal ceroid-lipofuscinoses (NCL) were studied by starch gel electrophoresis. After electrophoresis the gel was incubated with 4-methyl umbelliferyl phosphate at pH 4.5 and the fluorescent reaction product was visualized under ultraviolet light. Control brain showed a single band with mobility of about 1 cm while NCL patients showed two additional fast moving bands. In the late-infantile, and in the adult form (Kufs disease), the middle band was prominent while the fast moving band was predominant in juvenile NCL. In long-term lymphoblasts, controls showed a single band of acid phosphatase activity while both juvenile and late-infantile NCL showed two additional fast moving bands. Obligate heterozygotes showed reduced levels of the fast moving bands. Fluorometric assay of acid phosphatase using 4-methylumbelliferyl phosphate as substrate showed a 2-fold increase in activity in the patients. The increased acid phosphatase activity is completely inhibited by tartrate. Lymphocyte hexosamnidase activities were unchanged in NCL patients lymphoblasts. Studies on brains of NCL patients and on cultured lymphoblasts from families with late-infantile and juvenile form of NCL showed that abnormal acid phosphatase is characteristic of NCL.

Topics: Acid Phosphatase; Adolescent; Adult; beta-N-Acetylhexosaminidases; Brain; Cell Line; Cells, Cultured; Child, Preschool; Family; Gaucher Disease; Humans; Infant; Lymphocytes; Mucopolysaccharidosis III; Neuronal Ceroid-Lipofuscinoses; Substrate Specificity

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.

Topics: Acid Phosphatase; Adolescent; Adult; Anemia; Bone Diseases; Child; Child, Preschool; Gaucher Disease; Glucosylceramidase; Hepatomegaly; Humans; Kidney Diseases; Liver Diseases; Lung Diseases; Middle Aged; Peptidyl-Dipeptidase A; Splenectomy; Splenomegaly; Thrombocytopenia

Recently the intravenous enzyme replacement therapy with modified beta-glucocerebrosidase has become available for patients with M. Gaucher. We report here the considerable improvement of activity and vigor in a 5 year old girl with type 1 M. Gaucher administering 60 IU/kg every two weeks for 6 months. The platelet count increased from 82-96/nl to more than 150/nl and hemoglobin from 10.8 to more than 12 g/dl. Serum acid phosphatase decreased from 14.6 U/l to 5.9. U/l and angiotensin-converting enzyme from 327 to 102 U/l. The estimation of splenic volume by MRT showed a decrease by 40%, while liver size was not reduced within 6 months of therapy. MRT proved to be useful to demonstrate the bone marrow infiltration by Gaucher cells. The enzyme replacement therapy resulted in an objective response. No side effects have been observed so far. The extreme high treatment costs enforce a considerable dose reduction for maintenance therapy.

Topics: Acid Phosphatase; Alleles; Bone Marrow; Child, Preschool; Female; Gaucher Disease; Genotype; Glucosylceramidase; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Mutation; Peptidyl-Dipeptidase A

Bioptic material from the spleen of a three-year-old boy with a type 1 Gaucher disease was studied by immuno- and cytochemical methods with special regard to the macrophage-derived Gaucher cells. These cells were positive with PAS and Prussian blue staining, and were immuno-positive with the monoclonal 25 F9 antibody, specific to mature, non-inflammatory macrophages. Large Gaucher cells and their postulated small precursor cells revealed strong tartrate-resistant acid phosphatase (TRAP) and unspecific carboxylate esterase activities. Using a polyclonal antibody to bovine spleen purple phosphatase, a lysosomal TRAP from splenic macrophages, the TRAP of the Gaucher cells could be identified to belong to this group of iron-containing, purple acid phosphatases immunocytochemically. The origin of splenic Gaucher cells from blood monocytes and their further development are discussed.

Topics: Acid Phosphatase; Child, Preschool; Gaucher Disease; Humans; Immunohistochemistry; Male; Spleen; Tartrates

The purple acid phosphatases and uteroferrin belong to a diverse multifunctional class of binuclear iron-containing proteins that includes haemerythrin and ribonucleotide reductase. In the pig, uteroferrin has been implicated in the delivery of iron to the foetus, but the role of the related human type 5 acid phosphatase that is principally found in resident tissue macrophages is not yet clear. To define further the function of this metalloenzyme, we have isolated and sequenced a cDNA clone for type 5 acid phosphatase and investigated expression of its gene in human tissues. The phosphatase clone contains an open reading frame of 975 bp and encodes a protein of 325 amino acids, including a signal peptide of 19 residues and two potential sites for N-glycosylation. The type 5 acid phosphatase gene mapped to the short arm of human chromosome 19 and was found to have a restriction fragment length polymorphism on digestion with XbaI. Expression of phosphatase mRNA was restricted to mononuclear phagocytes and the enzyme was induced greater than 20-fold on transformation of normal human monocytes to macrophages by culture in serum-supplemented medium. Type 5 acid phosphatase thus represents a tightly regulated system for the study of molecular events in the differentiation programme of the normal macrophage.

Topics: Acid Phosphatase; Amino Acid Sequence; Base Sequence; Cell Differentiation; Cell Line; Cells, Cultured; Chromosome Mapping; DNA; DNA Probes; Gaucher Disease; Gene Amplification; Gene Expression; Gene Library; Humans; Immunoblotting; Isoenzymes; Lymphocytes; Macrophages; Molecular Sequence Data; Nucleic Acid Hybridization; Oligonucleotide Probes; Polymerase Chain Reaction; Restriction Mapping; Spleen; Transcription, Genetic

The authors studied an 18-year-old woman with stage IIIB nodular sclerosis Hodgkin's disease whose bone marrow contained abnormal storage cells that resembled Gaucher cells by light microscopic examination ("pseudo-Gaucher" cells). Electron microscopic examination revealed that these cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia. The patient's peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated, ruling out the diagnosis of inherited Gaucher's disease. After treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone), all signs of Hodgkin's disease and pseudo-Gaucher cells disappeared. Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged. The present case is unique with its documentation of classical enzyme patterns for beta-glucosidase and acid phosphatase and electron microscopic features. The authors postulate that pseudo-Gaucher cells result from excessive cell breakdown with an overload of available beta-glucosidase.

Topics: Acid Phosphatase; Adolescent; beta-Glucosidase; Bone Marrow; Diagnosis, Differential; Female; Gaucher Disease; Hodgkin Disease; Humans; Leukocytes; Microscopy, Electron; Neoplasm Staging

Plastic-embedded bone marrow biopsies from four patients with Gaucher's disease have been studied histochemically. Concanavalin A (ConA) was found to bind to cytoplasmic inclusions of Gaucher cells; the binding was prevented by lipid extraction or beta-glucosidase digestion. This suggests that glucocerebrosides stored in Gaucher cells are responsible for ConA binding; ConA staining combined with lipid extraction and beta-glucosidase digestion tests may be taken as a tool for the demonstration of Gaucher's cerebrosides of possible practical importance in diagnosis and investigation of Gaucher's disease. An excess of vic-glycol groups with respect to ConA binding-sugar residues and not extractable by lipid solvents are demonstrable in Gaucher cells. Vic-glycols appear to be regularly arranged at the electron microscopy level within Gaucher cell lysosomes along typical Gaucher "tubules", where some kind of interaction between lipid and protein should occur. Acid phosphatase might be one protein species involved in such interaction.

Topics: Acid Phosphatase; beta-Glucosidase; Bone Marrow; Concanavalin A; Gaucher Disease; Glucosylceramides; Histocytochemistry; Humans; Inclusion Bodies; Lysosomes; Methenamine; Microscopy, Electron; Periodic Acid; Silver; Staining and Labeling

Cytochemical studies were performed on peripheral blood from 30 patients with type 1 Gaucher disease. In 29 of the patients, peripheral blood monocytes stained positively for tartrate-resistant acid phosphatase, whereas monocytes from 18 normal individuals and 14 patients with monocytosis did not. In the Gaucher patients, the percentage of monocyte positivity for tartrate-resistant acid phosphatase ranged from 2 to 97. There was no correlation between the percent monocyte staining and the degree of disease severity, as measured by hepatosplenomegaly, pancytopenia, or extent of bone disease, for the group as a whole. In Gaucher patients who had not undergone splenectomy, however, there was a significant correlation between percent monocyte staining and the degree of hepatosplenomegaly, anemia, and thrombocytopenia. The presence of tartrate-resistant acid phosphatase may be secondary to the lysosomal accumulation of glucosyl ceramide within these monocytes, although this remains to be confirmed. If so, these circulating cells may represent precursors of the Gaucher cells in tissues. Tartrate-resistant acid phosphatase staining of peripheral blood monocytes may be useful as a diagnostic marker for Gaucher type 1 disease and for further studies on the pathogenesis of the disease.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Gaucher Disease; Hemoglobinometry; Hepatomegaly; Humans; Male; Middle Aged; Monocytes; Platelet Count; Splenectomy; Tartrates

Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non-neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520-711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5-15.5% of normal) and acid beta-glucosidase (13.8-27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 +/- 0.1 mM for controls and 0.6 +/- 0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents.

Topics: Acid Phosphatase; Adult; Bone Diseases; Electrophoresis, Polyacrylamide Gel; Female; Fibroblasts; Gaucher Disease; Glucosidases; Glucosylceramidase; Heterozygote; Humans; Kinetics; Lymphocytes; Male; Middle Aged

In this work we have studied the leucocytes and sera of 3 Gaucher patients, 4 obligate heterozygotes, 11 brothers and sisters of patients and 11 controls. Beta-glucosidase activity with 4-M-U-beta-glucopyranoside has been assayed at different pH's, in the presence of pure sodium taurocholate. At pH 4.5 and 5.0 sodium taurocholate activates the beta-glucosidase of control leucocytes, but inhibits the residual enzyme present in Gaucher leucocytes. The ratio of beta-glucosidase activity in the presence and absence of this effector seems to be a good approach to the diagnosis of Gaucher disease and it has proved indispensible in one patient's diagnosis. The apparent Km of beta-glucosidase determined for the same substrate, at pH 4.5 and 5.5 in the presence of sodium taurocholate showed markedly lower values in the patients than in the controls. An increased serum acid phosphatase activity, previously described as a secondary alteration in Gaucher disease, has also been studied and seems to be a useful complementary test, particularly when its age dependence is taken into account.

Topics: Acid Phosphatase; Adolescent; Adult; beta-Glucosidase; Child; Child, Preschool; Clinical Enzyme Tests; Female; Gaucher Disease; Genetic Carrier Screening; Glucosidases; Humans; Hydrogen-Ion Concentration; Kinetics; Leukocytes; Male; Substrate Specificity; Taurocholic Acid

Serum acid phosphatase activity has been used as a complementary test for the diagnosis of Gaucher's disease. This study suggests that phosphatase activity is age dependent. The use of controls in the patients' age is strongly recommended.

Topics: Acid Phosphatase; Adult; Aging; Child; Child, Preschool; Female; Gaucher Disease; Humans; Male; Mercaptoethanol; Quality Control; Reference Values; Sex Factors

An acid phosphatase species which was activated by Fe2+ was determined to be partially soluble but mainly particulate in rat spleen. The particulate enzyme could be extracted into 1 M KCl. This enzyme bound to Cibacron Blue-immobilized Sepharose (Blue-Sepharose) and was desorbed by 2 M KCl with a good yield, while the other acid phosphatases in rat spleen did not adsorb on Blue-Sepharose. The enzymes eluted on Blue-Sepharose chromatography of both the soluble and particulate fractions were electrophoretically identical. The enzyme hydrolyzed aryl monophosphates, phosphoproteins, and nucleoside di- and triphosphates. The activity for the three kinds of substrate was similarly activated by Fe2+, ascorbic acid and cysteine, and inhibited by molybdate, Cu2+ and F-. Cibacron Blue inhibited the enzyme competitively with respect to a substrate, p-nitrophenyl phosphate, but kinetic analysis suggested that more than one dye molecule binds to the enzyme. The Blue-Sepharose technique could be applied not only to quantitative separation of acid phosphatases similar to the spleen enzyme from bone and epidermis of rat, but also to that of a tartrate-resistant acid phosphatase from human spleen with Gaucher's disease.

Topics: Acid Phosphatase; Animals; Chromatography, Affinity; Gaucher Disease; Humans; Iron; Kinetics; Rats; Reference Values; Sepharose; Spleen

Although reduced acid beta-glucosidase activity appears to be the primary enzyme defect in type I Gaucher disease, patients with this disorder also have marked elevation of serum acid phosphatase and beta-hexosaminidase activities but with a normal level of lactic dehydrogenase activity. Moreover, there is a characteristic alteration in the hexosaminidase isozyme distribution with a striking increase in hexosaminidase B. Since these changes appear to be consistent and unlike those associated with other disorders or the hormonally induced alterations associated with pregnancy, routine serum testing for the Tay-Sachs carrier state may offer a useful approach for the presumptive diagnosis and screening for Gaucher disease. Unlike the changes in affected homozygotes, there are no characteristic alterations of acid phosphatase or hexosaminidase in heterozygotes for Gaucher disease.

Topics: Acid Phosphatase; Diabetes Mellitus, Type 1; Female; Gaucher Disease; Genetic Carrier Screening; Hexosaminidases; Humans; Pregnancy; Tay-Sachs Disease

Topics: Acid Phosphatase; Adult; Bone Diseases; Child; Child, Preschool; Colorimetry; Electrophoresis, Polyacrylamide Gel; Gaucher Disease; Humans; Immunoenzyme Techniques; Infant; Middle Aged; Splenectomy; Tartrates

Topics: Acid Phosphatase; Animals; beta-Glucosidase; Brain; Cerebrosides; Disease Models, Animal; Galactosylceramides; Gangliosides; Gaucher Disease; Humans; Inositol; Mice; Myelin Sheath; Spleen

Electrophoresis and ion-exchange column chromatography were used to separate the wide varieties of acid phosphatases with different biological and clinical significance. Band 0 was very strong in ascitic cells with many autophagic vacuoles, indicating a role in autophagic function. Band 1 was a membrane-bound acid phosphatase, seen mainly in the microsomal fraction. Band 3 was the major lysosomal acid phosphatase of all nonprostatic tissues. Bands 2 and 4 were antigenically identical to each other, and were observed in unusually high amounts in the prostate. The different electrophoretic mobility between bands 2 and 4 was due to their carbohydrate content. Band 5 was a characteristic enzyme of the osteoclast. The tartrate-sensitive enzymes included bands 0 through 4. Only band 5 was tartrate resistant. The tartrate-resistant acid phosphatase of erythrocytes was not detected by the electrophoresis method. Clinical applications were seen for both bands 2 and 5. Band 2 was a secretory enzyme, normally secreted into the seminal plasma. Band 2 was absorbed into the blood circulation in some prostatic cancer patients. A small amount of bands 2 and 4 was observed in nonprostatic tissues. The diagnostic value of band 2 resulted from its extremely high concentration in the prostate. Band 5 was not observed in the normal prostate. A high concentration of band 5 was observed in hairy cells, Gaucher cells, and osteoclasts. The serum level of band 5b was an indicator of osteoclastic activity in the bone. Elevation of band 5b in serum was observed in normal children during physiological bone growth, in Gaucher's disease, and in malignancies metastasized to bone.

Topics: Acid Phosphatase; Animals; Ascites; Bone Neoplasms; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Gaucher Disease; Humans; Leukemia L1210; Male; Mice; Osteoclasts; Phagocytes; Prostate; Prostatic Neoplasms; Tartrates

The Gaucher cell results from the accumulation of excessive glucocerebroside in cells of the monocyte-macrophage system. It is characterized ultrastructurally by the presence of cytoplasmic inclusions which consist of tubule-like structures measuring 130 to 150 Ao in diameter. Utilizing freeze fracture and x-ray diffraction techniques these structures appear to be bilayers measuring 6 nm in thickness, 40 to 60 nm wide and up to 600 nm in length. The Gaucher cell contains isoenzyme 5 of acid phosphatase which is resistant to prior incubation in tartaric acid. The bone marrow smears from patients with Gaucher's disease contain monocytes and monocytoid cells which contain inclusions which are acid phosphatase positive and resemble the acid phosphatase positive inclusions in the Gaucher cells. Ultrastructural studies of monocytes from Gaucher patients demonstrated membrane-bound inclusions containing tubule-like structures identical to those in Gaucher cells. These monocytic cells appear to represent precursors of Gaucher cells.

Topics: Acid Phosphatase; Bone Marrow; Carboxylesterase; Carboxylic Ester Hydrolases; Gaucher Disease; Histocytochemistry; Humans; Leukemia; Macrophages; Monocytes

Topics: Acid Phosphatase; Adolescent; Adult; Child; Child, Preschool; Gaucher Disease; Humans; Male; Splenectomy

Topics: Acid Phosphatase; Female; Gaucher Disease; Humans; Hydrogen-Ion Concentration; Isoenzymes; Peptidyl-Dipeptidase A

The physician who diagnoses Gaucher's disease should take advantage of the noninvasive method that analyzes WBCs for residual beta-glucocerebrosidase and beta-glucosidase activities. When this method is carried out in conjunction with the measurement of serum acid phosphatase levels, a bone marrow examination may be unnecessary. With this method, we studied an adult who had mild splenomegaly and abdominal pain. When bone marrow was finally obtained subsequent to diagnosis by the enzymatic analysis, the deposits that are specifically formed in Gaucher's disease were easily demonstrated by electron microscopy. We believe that these methods are more specific for the diagnosis of Gaucher's disease than is the light microscopic finding of bone marrow cells that have abundant and striated cytoplasm.

Topics: Acid Phosphatase; beta-Glucosidase; Bone Marrow; Clinical Enzyme Tests; Female; Gaucher Disease; Glucosylceramidase; Glucuronidase; Humans; Leukocytes; Middle Aged

Tartrate-resistant acid phosphatase was isolated from serum and spleen of patients affected by Gaucher's disease. Electrophoretic and antigenic properties were compared to the enzyme isolated from hairy cells described in a previous study (9). The enzyme isolated from Gaucher serum has electrophoretic and antigenic properties identical to the acid phosphatase band 5b of hairy cells. The major tartrate-resistant acid phosphatase in the Gaucher spleen is band 5a. Bands 5a and 5b have identical protein structure indicated by their identical antigenicity. The removal of carbohydrate from band 5a by sialidase converted band 5a to 5b.

Topics: Acid Phosphatase; Adolescent; Adult; Blood Protein Electrophoresis; Child; Child, Preschool; Colorimetry; Female; Gaucher Disease; Humans; Immunodiffusion; Leukemia, Hairy Cell; Male; Middle Aged; Molecular Weight; Tartrates

The activity of acid hydrolases was studied in serum from patients with mucolipidosis (II and III) and other lysosomal disorders. In mucolipidosis II and III all hydrolases examined except alpha-glucosidase, beta-glucosidase and acid phosphatase were greatly increased. High values for beta-galactosidase were seen in mucopolysaccharidosis types I and II, Gaucher's disease, juvenile amaurotic idiocy and metachromatic leucodystrophy. N-Acetyl-beta-glucosaminidase activity was high in mucopolysaccharidosis types I, II, III and Gaucher's disease. The activity of beta-glucuronidase was increased in mucopolysaccharidosis types I, II and III, Gaucher's disease, juvenile amaurotic idiocy and metachromatic leucodystrophy. Acid phosphatase had increased activity only in Gaucher's disease. In several lysosomal storage disorders no increased values could be found. It is suggested that high values in serum from patients with lysosomal storage disorders (not including mucolipidosis II and III) may depend upon liver cell damage, which disturbs the clearing of acid hydrolases from serum.

Topics: Acid Phosphatase; Gaucher Disease; Glycoside Hydrolases; Humans; Leukodystrophy, Metachromatic; Lipidoses; Lysosomes; Metabolism, Inborn Errors; Mucopolysaccharidoses

We discuss the clinical features of two patients with type 3 Gaucher's disease. Glucocerebroside levels in liver biopsy specimens were measured in both patients and the findings are discussed in regard to the pathogenesis of the disease.

Topics: Acid Phosphatase; Adolescent; Adult; Epilepsies, Myoclonic; Gaucher Disease; Glucosylceramides; Humans; Liver; Male; Myoclonus

Topics: Acid Phosphatase; Adult; Gaucher Disease; Glycoproteins; Humans; Isoenzymes; Kinetics; Molecular Weight; Spleen; Substrate Specificity; Tartrates

Topics: Acid Phosphatase; Child; Female; Gaucher Disease; Humans; Isoenzymes; Kinetics; Molecular Weight; Splenic Diseases; Tartrates

A family is described in which adult-onset Gaucher's disease developed, followed years later by atypical psychotic disorders with neurologic and electroencephalographic abnormalities. A biochemical investigation of primary and secondary enzyme alterations in the index case was performed in an attempt to identify a pattern that might be specific to this clinical profile. The literature pertaining to CNS involvement in adult patients with Gaucher's disease is also reviewed. An etiologic link may exist between the inherited metabolic disorder and associated neuropsychiatric impairment. The biochemical basis of this hypothesized association remains unclear, however, and further enzymatic and pathologic investigations are warranted.

Topics: Acid Phosphatase; Adult; Basal Ganglia Diseases; Epilepsy; Female; Gaucher Disease; Glucosidases; Glucosylceramidase; Glucosylceramides; Humans; Leukocytes; Male; Middle Aged; Neurocognitive Disorders

Topics: Acid Phosphatase; Adult; Bone Marrow; Female; Gaucher Disease; Humans; Spleen; Tartrates

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Bone Neoplasms; Diagnosis, Differential; Femoral Neoplasms; Gaucher Disease; Humans; Kidney Neoplasms; Male; Neoplasm Metastasis; Ribs

Topics: Acid Phosphatase; Animals; Brain; Cerebrosides; Disease Models, Animal; Gangliosides; Gaucher Disease; Humans; Inositol; Liver; Mice; Spleen; Xylosidases

Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to those of the major acid phosphatase activity observed to be present in serum of patients with Gaucher's disease. These data indicate that simple spleen spillage cannot account for the increased levels of serum acid phosphatase in patients with Gaucher's disease.

Topics: Acid Phosphatase; Adult; Child; Child, Preschool; Chromatography, Ion Exchange; Dithionite; Fluorides; Gaucher Disease; Humans; Hydrogen-Ion Concentration; Hymecromone; Infant; Isoenzymes; Macromolecular Substances; Mercaptoethanol; Organophosphorus Compounds; Spleen; Tartrates

An immunochemical method for detection of prostatic acid prosphatase is described. Purified acid phosphatase was isolated from cancerous human prostate. A specific antiserum to the purified enzyme was produced in rabbits. The antiserum to postatic acid phosphatase did not react with acid phosphatase originating from other tissues. A counter immunolectrophoresis, utilizing the specific antibodies and a chemical staining technique, has been developed and clinically evaluated. Sera from patients with prostatic carcinoma (6/20 of stage B, 27/49 of stage C, and 98/125 of stage D) gave positive results. Sera from 19 patients with benign prostatic hypertrophy, from 89 patients with other tumors, from 12 patients with Gaucher's disease, from 107 healthy volunteers, and from 50 normal age-matched men all gave negative results. The sensitivity of this method was 0.4 IU of enzyme activity or 20 ng per ml of prostatic acid phosphatase protein. Further clinical evaluation of patients in the early stage of prostatic cancer and of patients undergoing chemotherapy is in progress.

Topics: Acid Phosphatase; Animals; Chemical Phenomena; Chemistry; Counterimmunoelectrophoresis; Female; Gaucher Disease; Humans; Immune Sera; Male; Prostatic Neoplasms; Rabbits; Staining and Labeling

Topics: Acid Phosphatase; Adult; beta-Glucosidase; Brain; Child; Child, Preschool; Gaucher Disease; Glucosylceramidase; Humans; Hydrolases; Infant; Liver; Lysosomes; Spleen

Topics: Acid Phosphatase; Enzyme Activation; Gaucher Disease; Glucosidases; Glucosylceramidase; Glycoproteins; Humans; Lysosomes; Spleen; Subcellular Fractions

The isoenzymes of human prostatic acid phosphatase have been studied by an isoelectric focusing technique. Purified acid phosphatase from malignant prostates contained eight isoenzymes with pI 4.4--5.3. The sera from patients with prostate cancer were shown to have similar acid phosphatase isoenzyme patterns at pI 4.0--5.5; as the serum enzyme activities increased, the pI of isoenzymes shifted to more acidic pH. These isoenzyme patterns of sera from patients with prostate cancer were different from those of patients with Gaucher's disease or from acid phosphatase of human erythrocytes, both of which exhibited only one enzyme band around pI 5.0 and 6.0, respectively. Treatment of serum sample of prostate cancer with neuraminidase did not result in a single enzyme band but alter the pI of isoenzymes, which shifted to a higher pH region. The significance of acid phosphatase activities and its isoenzyme patterns in prostate cancer merits further investigation.

Topics: Acid Phosphatase; Gaucher Disease; Humans; Isoelectric Focusing; Isoenzymes; Male; Neuraminidase; Prostatic Neoplasms

We describe a new assay that is useful for identifying individuals who may be affected with Gaucher's disease. The assay involves the determination of serum acid phosphatase activity using the fluorogenic substrate 4-methylumbelliferyl phosphate. The assay measures acid phosphatase activity at pH 6.0 in the presence of 3.0 M 2-mercaptoethanol and requires a 5 microliter serum sample and a 15-min incubation period. Under these conditions, 2-mercaptoethanol preferentially inhibited the acid phosphatase activity in control serum but did not inhibit the elevated acid phosphatase present in the serum of patients with Gaucher's disease. Using this assay, we observed a 5-50-fold elevation in serum acid phosphatase activity in 8 patients with the adult, non-neuropathic form of Gaucher's disease when compared to control serum assayed under the same conditions. Serum from several heterozygotes free from pathology exhibited normal acid phosphatase activity when assayed at pH 6.0 in the presence of 2-mercaptoethanol. Acid phosphatase activity in serum from patients with prostatic cancer can be distinguished from that in Gaucher serum on the basis of the well-documented sensitivity of the former to inhibition by sodium tartrate. A serum sample from a patient with Niemann-Pick disease exhibited a mild elevation in tartrate-resistant acid phosphatase activity so that conclusive diagnosis of Gaucher's disease requires assaying leukocytes or fibroblasts from suspected patients for glucocerebroside:beta-glucosidase activity.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Female; Fluorometry; Gaucher Disease; Humans; Hydrogen-Ion Concentration; Hymecromone; Male; Mercaptoethanol; Middle Aged; Spectrophotometry; Umbelliferones

A patient with far-advanced adult type Gaucher's disease was treated with solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection. In some instances the enzyme-containing erythrocytes were coated with gamma globulin. No toxic side effects were observed after enzyme infusion. There were suggestive, but not conclusive, findings that enzyme infusion may have been beneficial. After therapy, there was a decrease in transfusion requirement, some improvement of liver function, possible decrease in liver size, and relief of subjective symptoms. Erythrocyte and plasma glucocerebroside levels were unchanged during therapy, but there was a possibly significant decrease in leukocyte and platelet levels of the glycolipid. No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity.

Topics: Acid Phosphatase; Adult; Alanine Transaminase; Aspartate Aminotransferases; Blood Cell Count; Female; Gaucher Disease; Glucosidases; Glucosylceramidase; Humans; Liver; Organ Size; Peptidyl-Dipeptidase A; Placenta; Radionuclide Imaging; Time Factors

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Bone Marrow; Brain; Cerebrosides; Child; Child, Preschool; Diagnosis, Differential; Female; Gaucher Disease; Glucosylceramidase; Humans; Infant; Iron; Lipid Metabolism; Liver; Lung; Lymph Nodes; Lysosomes; Male; Middle Aged; Splenomegaly

Acid phosphatase (EC 3.1.3.2) isoenzyme profiles of extracts of splenic tissue and serum from patients with Gaucher's disease were measured by a mini-column ion-exchange chromatographic method [Clin. Chem., 23, 000 (1977)]. Diagnosis of Gaucher's disease in the five patients studied was confirmed by demonstrating decreased (2.3 to 4.1% of normal) glucocerebrosidase activity in the spleen. With p-nitrophenyl phosphate as substrate, increased acid phosphatase activity (three-to eight-fold normal) was demonstrated in spleen tissue from Gaucher;s disease patients; isoenzyme profiles by the ion-exchange column technique showed acid phosphatase isoenzyme 5 to be the predominant isoenzyme. Comparison of acid phosphatase isoenzyme profiles from patients with Gaucher's disease and prostatic carcinoma revealed distinct differences in the activities of isoenzymes 2 and 5. The isoenzyme-5 measurement thus appears to provide a diagnostic test for Gaucher's disease that can be done reapidly and easily in the routine clinical chemistry laboratory.

Topics: Acid Phosphatase; Adult; Aged; Child; Child, Preschool; Chromatography, Ion Exchange; Female; Gaucher Disease; Glucosylceramidase; Humans; Infant; Isoenzymes; Lysosomes; Male; Spleen

Topics: Acid Phosphatase; Adult; Amino Acids; Child; Child, Preschool; Enzyme Activation; Female; G(M1) Ganglioside; Galactosidases; Gaucher Disease; Glucosidases; Glucosylceramidase; Glycoproteins; Hot Temperature; Humans; Infant; Male; Molecular Weight; Spleen

Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: "acid" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested.

Topics: Acid Phosphatase; Blood Platelets; Fabry Disease; Galactosidases; Gaucher Disease; Glucosidases; Glucuronidase; Glycoside Hydrolases; Granulocytes; Hexosaminidases; Humans; Hydrogen-Ion Concentration; Leukocytes; Lymphocytes; Lysosomes; Mannosidases; Monocytes

Topics: Acid Phosphatase; Anemia, Hypochromic; Bone Marrow; Bone Marrow Cells; Cell Nucleus; Cytoplasm; Gaucher Disease; Histiocytes; Humans; Leukemia, Myeloid; Leukemoid Reaction; Lipids; Organoids; Staining and Labeling

Topics: Acid Phosphatase; Adult; Female; Gaucher Disease; Humans; Male; Peptidyl-Dipeptidase A; Sarcoidosis

Topics: Acid Phosphatase; Adult; Blood Platelets; Female; Galactosidases; Gaucher Disease; Glucuronidase; Hexosaminidases; Humans; Lysosomes; Male; Splenomegaly; Thrombin

Topics: Acid Phosphatase; Adult; Blood Platelets; Bone Marrow Examination; Cell Count; Clinical Enzyme Tests; Gaucher Disease; Glucosidases; Hemoglobinometry; Humans; Hydrogen-Ion Concentration; Leukocyte Count; Leukocytes; Male; Spleen; Splenectomy

Topics: Acid Phosphatase; Adolescent; Adult; Bone Marrow; Child, Preschool; Epidermal Cyst; Esterases; Female; Gaucher Disease; Histocytochemistry; Humans; Infant; Liver; Lymph Nodes; Male; Microscopy, Electron; Middle Aged; Spleen; Splenic Diseases

Topics: Acid Phosphatase; Adolescent; Adult; Bone Marrow; Bone Marrow Cells; Child; Female; Gaucher Disease; Histiocytes; Humans; Inclusion Bodies; Lactose Intolerance; Male; Pedigree; Peripheral Nervous System Diseases; Pigmentation Disorders; Splenomegaly; Staining and Labeling; Syndrome

Topics: Acid Phosphatase; Adolescent; Bone Marrow; Gaucher Disease; Humans; Lymphatic Diseases; Male

Topics: Acid Phosphatase; Adult; Cells; Diagnosis, Differential; Gaucher Disease; Histocytochemistry; Humans; Inclusion Bodies; Leukemia, Myeloid; Leukocytes; Lipids; Male; Microscopy, Electron; Mononuclear Phagocyte System; Phagocytosis; Reticulocytes; Staining and Labeling

Topics: Acid Phosphatase; Cerebrosides; Chromatography, Thin Layer; Clinical Enzyme Tests; Gaucher Disease; Glucosidases; Humans; Hydrogen-Ion Concentration; Leukocytes; Lipids; Neurologic Manifestations

Topics: Acid Phosphatase; Cells, Cultured; Culture Media; Diploidy; Fibroblasts; Gaucher Disease; Glucosidases; Histocytochemistry; Humans; In Vitro Techniques; Lipid Metabolism, Inborn Errors; Lysosomes; Metabolism, Inborn Errors; Skin; Sulfatases

Topics: Acid Phosphatase; Adult; Biopsy; Blood Cell Count; Blood Coagulation Tests; Blood Protein Electrophoresis; Blood Sedimentation; Bone Marrow Cells; Chronic Disease; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Haptoglobins; Hemoglobinometry; Humans; Male; Osmotic Fragility; Splenomegaly; Thrombocytopenia

Topics: Acid Phosphatase; Adult; Age Factors; Autopsy; Brain Chemistry; Chronic Disease; Electroencephalography; Epilepsy, Tonic-Clonic; Fatty Acids; Gaucher Disease; Glomerulonephritis; Hepatomegaly; Histocompatibility; Humans; Hypertension, Renal; Immunosuppressive Agents; Kyphosis; Liver; Male; Muscular Atrophy; Nephrectomy; Pneumonia; Radionuclide Imaging; Sphingolipids; Spleen; Transplantation, Homologous

Topics: Acid Phosphatase; Blood Platelets; Bone Marrow; Bone Marrow Cells; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Electrophoresis, Disc; Fluorides; Gaucher Disease; Histocytochemistry; Humans; Isoenzymes; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Lymphatic Diseases; Lymphocytes; Lymphoma, Non-Hodgkin; Molecular Weight; Monocytes; Nitrophenols; Polycythemia Vera; Staining and Labeling; Tartrates

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Cell Membrane; Cytoplasm; Cytoplasmic Granules; Erythrocytes; Esterases; Female; Gaucher Disease; Golgi Apparatus; Histocytochemistry; Humans; Phagocytosis; Phosphoric Monoester Hydrolases; Spleen

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Carcinoma; Female; Gaucher Disease; Humans; Hyperparathyroidism; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Esterases; Female; Gaucher Disease; Humans; Phagocytosis; Polysaccharides; Reticulocytes; Staining and Labeling

Topics: Acid Phosphatase; Adult; Aged; Gaucher Disease; Histocytochemistry; Humans; Male; Middle Aged

Topics: Acid Phosphatase; Bone Marrow Examination; Cerebrosides; Female; Gaucher Disease; Glycoside Hydrolases; Humans; Leukemia, Myeloid; Leukocytes; Lipids; Liver; Lymph Nodes; Microscopy, Electron; Middle Aged; Spleen

Topics: Acid Phosphatase; Adult; Aged; Blood Platelet Disorders; Bone Diseases; Bone Neoplasms; Female; Gaucher Disease; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Child, Preschool; Culture Techniques; Female; Gaucher Disease; Humans; Spleen

Topics: Acid Phosphatase; Cerebrosides; Child, Preschool; Culture Techniques; Female; Gaucher Disease; Histocytochemistry; Humans; Periodic Acid; Skin; Spleen

Topics: Acid Phosphatase; Electrophoresis, Disc; Female; Gaucher Disease; Hot Temperature; Humans; Isoenzymes; Liver; Lymph Nodes; Male; Multiple Myeloma; Prostate; Prostatic Neoplasms; Spleen

Topics: Acid Phosphatase; Adult; Brain; Child; Galactosidases; Gaucher Disease; Glucosidases; Glycoside Hydrolases; Humans; Liver; Lysosomes; Spleen

Topics: Acid Phosphatase; Child; Child, Preschool; Female; Gaucher Disease; Humans; Lipids; Liver; Male

Topics: Acid Phosphatase; Densitometry; Electrophoresis; Female; Gaucher Disease; Humans; Isoenzymes; Male; Multiple Myeloma; Prostatic Neoplasms

Topics: Acid Phosphatase; Electrophoresis; Gaucher Disease; Glycerophosphates; Humans; Hyperparathyroidism; Male; Osteopetrosis; Phosphates; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Cell Biology; Cholecystitis; Cholelithiasis; Electrons; Esterases; Gaucher Disease; Genetics, Medical; Histocytochemistry; Humans; Jaundice; Leukocytes; Microscopy; Microscopy, Electron; Splenectomy; Sulfatases

Topics: Acid Phosphatase; Anemia; Anemia, Aplastic; Blood Cell Count; Blood Platelets; Bone Marrow Examination; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Geriatrics; Humans; Liver Cirrhosis; Pathology; Phosphates; Splenomegaly

Topics: Acid Phosphatase; Adolescent; Blood Platelets; Child; Copper; Enzyme Inhibitors; Erythrocytes; Formaldehyde; Gaucher Disease; Genetics, Medical; Humans; Megakaryocytes; Pharmacology; Statistics as Topic; Sulfates; Sweden

Topics: Acid Phosphatase; Bone Marrow Examination; Gaucher Disease; Histocytochemistry; Humans; Spleen

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteogenesis Imperfecta; Osteopetrosis; Osteosclerosis; Prostatic Neoplasms

Topics: Acid Phosphatase; Gaucher Disease; Humans; Lipidoses; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Gaucher Disease; Lipidoses; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Disease; Gaucher Disease; Humans; Lipidoses; Male; Phosphoric Monoester Hydrolases; Prostate; Prostatic Diseases; Prostatism