allopurinol and Purine-Pyrimidine-Metabolism--Inborn-Errors

Topics: Carrier Proteins; Diagnosis, Differential; Humans; Kidney Tubules; Mutation; Organic Anion Transporters; Organic Cation Transport Proteins; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Creatinine; Humans; Inappropriate ADH Syndrome; Kidney Diseases; Kidney Tubules; Losartan; Metabolic Clearance Rate; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Coenzymes; Diagnosis, Differential; Humans; Liver Diseases; Metalloproteins; Molybdenum Cofactors; Prognosis; Pteridines; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Xanthine

Topics: Adenylosuccinate Lyase; Allopurinol; Humans; Lesch-Nyhan Syndrome; Psychomotor Disorders; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Self Mutilation

Topics: Aldehyde Oxidase; Aldehyde Oxidoreductases; Amino Acid Metabolism, Inborn Errors; Coenzymes; Diagnosis, Differential; Humans; Metalloproteins; Molybdenum Cofactors; Oxidoreductases Acting on Sulfur Group Donors; Prognosis; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase

Uric acid is the end product of purine metabolism in human. Then, the enzymatic abnormalities, concerning purine metabolism, cause disorders of uric acid metabolism including hyperuricemia and hypouricemia. The superactivity of 5-phosphoribosyl-pyrophosphate (PRPP) synthetase and deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) caused hyperuricemia. In glycogen storage diseases of type I, III, V, and VII, decreased energy supply induces hyperuricemia by accelerating ATP degradation. Deficiencies of xanthine oxidase (XO), purine nucleoside phosphorylase (PNP), and PRPP were reported causing hypouricemia. Many methods for DNA-diagnosis were developed including Southern blot, Northern blot, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism), PCR-RFLP (restriction fragment length polymorphism), and allele specific oligonucleotide hybridization etc.

Topics: Adenosine Triphosphate; DNA; Humans; Hypoxanthine Phosphoribosyltransferase; Molecular Probe Techniques; Nucleic Acid Hybridization; Phosphoribosyl Pyrophosphate; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Xanthine Oxidase

Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.

Topics: Central Nervous System Diseases; Coenzymes; Diagnosis, Differential; Diet Therapy; Humans; Infant, Newborn; Metalloproteins; Molybdenum Cofactors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid; Xanthine; Xanthine Oxidase; Xanthines

Topics: Adenine Phosphoribosyltransferase; Adolescent; Adult; Allopurinol; Child; Child, Preschool; Diet; Female; Genotype; Humans; Infant; Japan; Male; Middle Aged; Mutation; Phenotype; Purine-Pyrimidine Metabolism, Inborn Errors; Urinary Calculi

There has been an explosion of knowledge in disorders of purine and pyrimidine metabolism during the last 20 years. During this time, more than 10 diseases have been discovered and their metabolic bases studied. Hyperuricemia and gout remain the most common clinical disorder. Rarely these disorders are explainable by an inherited enzyme abnormally, such as hypoxanthine-guanine phosphoribosyltransferase deficiency, phosphoribosyl-pyrophosphate synthetase deficiency, or glucose-6-phosphatase deficiency. The description of immunodeficiency syndromes in association with purine enzyme deficiency has led to a novel area of investigation encompassing the biochemical basis for immune function. Although less information is available concerning the other diseases associated with renal calculi, myopathy, anemia, and central nervous system dysfunction, further research will elucidate important metabolic relationships. These will no doubt expand our understanding of the pathogenesis of these disorders and provide innovative therapeutic approaches.

Topics: 5'-Nucleotidase; Adenine Phosphoribosyltransferase; Adenosine Deaminase; AMP Deaminase; Gout; Guanine Deaminase; Humans; Hypoxanthine Phosphoribosyltransferase; Immunologic Deficiency Syndromes; Nucleotidases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Xanthine Oxidase

Topics: 5'-Nucleotidase; Adenine Phosphoribosyltransferase; Adenosine Deaminase; Amidophosphoribosyltransferase; AMP Deaminase; Genes; Humans; Hypoxanthine Phosphoribosyltransferase; Lesch-Nyhan Syndrome; Nucleotidases; Orotic Acid; Oxidoreductases Acting on Sulfur Group Donors; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Xanthine Oxidase

Topics: Acute Disease; Allopurinol; Arthritis; Aspirin; Colchicine; Coronary Disease; Diuretics; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Indomethacin; Kidney; Kidney Calculi; Kidney Diseases; Lead Poisoning; Lymphoproliferative Disorders; Myeloproliferative Disorders; Phenylbutazone; Platelet Aggregation; Probenecid; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Uricosuric Agents

Topics: Acute Kidney Injury; Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Diagnosis, Differential; Diet; Heterozygote; Homozygote; Humans; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Urinary Calculi

Topics: Adult; Alcoholism; Cholesterol, Dietary; Chylomicrons; Diet, Reducing; Dietary Fats; Female; Gout; Humans; Hyperlipidemias; Purine-Pyrimidine Metabolism, Inborn Errors; Triglycerides; Uricosuric Agents; Xanthine Oxidase

Pyrimidine synthesis and its regulation are presented. Among the disorders of human pyrimidine metabolism, hereditary orotic aciduria and that produced by drugs play the principal role. A rise in renal excretion of orotic acis is also observed when ornithine transcarbamylase activity is lacking. The importance of "orotic aciduria with partial response to folic acid" in pyrimidine metabolism is still not clear. Close relationship between the formation of pyrimidine and purine nucleotides must be assumed, because both enter into the synthesis of nucleic acid, for the greatest part in approximately equimolecular amounts. Possibly 5-phosphoribosyl-1-pyrophosphate plays an important part.

Topics: Allopurinol; Azauridine; Chemical Phenomena; Chemistry; Cytidine; Folic Acid; Humans; Infant; Male; Ornithine Carbamoyltransferase; Orotic Acid; Phosphoribosyl Pyrophosphate; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidine Nucleotides; Pyrimidines; Uridine

Topics: Adenine Nucleotides; Anemia, Hemolytic, Congenital Nonspherocytic; Glutamate Dehydrogenase; Glutaminase; Glutathione Reductase; Glycogen Storage Disease; Gout; Guanine Nucleotides; Humans; Hypoxanthines; Immunologic Deficiency Syndromes; Kinetics; Lesch-Nyhan Syndrome; Molecular Weight; Mutation; Pentosephosphates; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Ribose; Species Specificity; Xanthine Oxidase; Xanthines

Topics: Amidophosphoribosyltransferase; Chemical Phenomena; Chemistry; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Gout; Humans; Inosine Monophosphate; Lesch-Nyhan Syndrome; Phosphoribosyl Pyrophosphate; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthine Oxidase; Xanthines; Xeroderma Pigmentosum

Topics: Allopurinol; Gout; Humans; Kidney; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Amniocentesis; Athetosis; Brain; Erythrocytes; Fibroblasts; Humans; Intellectual Disability; Lesch-Nyhan Syndrome; Male; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Uric Acid

Topics: Adenine; Adrenocorticotropic Hormone; Allopurinol; Animals; Glycogen; Gout; Humans; Lesch-Nyhan Syndrome; Methylene Blue; Orotic Acid; Pentosephosphates; Phosphoric Acids; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose; Thiadiazoles; Thyrotropin; Transferases; Urate Oxidase; Uric Acid

Topics: Allopurinol; Child; Child, Preschool; Female; Gas Chromatography-Mass Spectrometry; Gout Suppressants; Humans; Infant; Infant, Newborn; Male; Ornithine Carbamoyltransferase Deficiency Disease; Orotic Acid; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors

Topics: Adolescent; Adult; Aged; Allopurinol; Creatinine; Female; Follow-Up Studies; Humans; Hypertension; Kidney Diseases; Male; Pedigree; Prospective Studies; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Hereditary xanthinuria (type I) is caused by an inherited deficiency of the xanthine oxidorectase (XDH/XO), and is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine, leading to urolithiasis. Type II results from a combined deficiency of XDH/XO and aldehyde oxidase. Patients present with hematuria, renal colic, urolithiasis or even acute renal failure. Clinical symptoms are the same for both types. In a third type, clinically distinct, sulfite oxidase activity is missing as well as XDH/XO and aldehyde oxidase. The prevalence is not known, but about 150 cases have been described so far. Hypouricemia is sometimes overlooked, that´s why we have set up the diagnostic flowchart. This consists of a) evaluation of uric acid concentrations in serum and urine with exclusion of primary renal hypouricemia, b) estimation of urinary xanthine, c) allopurinol loading test, which enables to distinguish type I and II; and finally assay of xanthine oxidoreductase activity in plasma with molecular genetic analysis. Following this diagnostic procedure we were able to find first patients with hereditary xanthinuria in our Czech population. We have detected nine cases, which is one of the largest group worldwide. Four patients were asymptomatic. All had profound hypouricemia, which was the first sign and led to referral to our department. Urinary concentrations of xanthine were in the range of 170-598 mmol/mol creatinine (normal < 30 mmol/mol creatinine). Hereditary xanthinuria is still unrecognized disorder and subjects with unexplained hypouricemia need detailed purine metabolic investigation.

Topics: Adult; Aldehyde Oxidase; Allopurinol; Child; Child, Preschool; Czech Republic; Diagnosis, Differential; Humans; Metabolism, Inborn Errors; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Renal Tubular Transport, Inborn Errors; Uric Acid; Urinary Calculi; Xanthine; Xanthine Dehydrogenase

The aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy.. During a routine biochemical follow-up of the patient, undetectable serum uric acid (<10 μl) was observed. A high performance liquid chromatography analysis of urinary purines revealed increased levels of xanthine (137 mmol/mol creatinine). The suspected diagnosis of hereditary xanthinuria, a rare autosomal recessive disorder of the last two steps of purine metabolism, was confirmed by sequence analysis.. An analysis of XDH/XO and AOX1 revealed common polymorphisms, while analysis of the MOCOS gene identified a rare homozygous variant c.362C > T. Dysfunction of this variant was confirmed by significantly decreased xanthine dehydrogenase/oxidase activity in the patient's plasma (<2% of control mean activity).. We present a biochemical, enzymatic, and molecular genetic case study suggesting an important association between a hitherto undescribed dysfunction variant in the MOCOS gene and thiopurine-induced toxicity. The identified variant c.362C > T results in slower thiopurine metabolism caused by inhibition of 6-mercaptopurine oxidation (catabolism) to 6-thioxanthine and 6-thiouric acid, which increases the formation of the nucleotide 6-thioguanine, which is toxic. This is the first clinical case to identify the crucial role of the MOCOS gene in thiopurine intolerance and confirm the impact of genetic variability of purine enzymes on different therapeutic outcomes in patients undergoing thiopurine treatment.

Topics: Adult; Aldehyde Oxidase; Female; Humans; Mercaptopurine; Methyltransferases; Polymorphism, Genetic; Purine-Pyrimidine Metabolism, Inborn Errors; Sulfurtransferases; Uric Acid; Xanthine; Xanthine Dehydrogenase; Xanthine Oxidase

Hypouricemia is caused by various diseases and disorders, such as hepatic failure, Fanconi renotubular syndrome, nutritional deficiencies and genetic defects. Genetic defects of the molybdoflavoprotein enzymes induce hypouricemia and xanthinuria. Here, we identified a patient whose plasma and urine uric acid levels were both extremely low and aimed to identify the pathogenic gene and verify its mechanism.. Using next-generation sequencing (NGS), we detected a mutation in the human molybdenum cofactor sulfurase (MCSU) gene that may cause hypouricemia. We cultured L02 cells, knocked down MCSU with RNAi, and then detected the uric acid and MCSU concentrations, xanthine oxidase (XOD) and xanthine dehydrogenase (XDH) activity levels, and xanthine/hypoxanthine concentrations in cell lysates and culture supernatants.. The NGS results showed that the patient had a mutation in the human MCSU gene. The in vitro study showed that RNAi of MCSU caused the uric acid, human MCSU concentrations, the XOD and XDH activity levels among cellular proteins and culture supernatants to be extremely low relative to those of the control. However, the xanthine/hypoxanthine concentrations were much higher than those of the control.. We strongly confirmed the pathogenicity of the human MCSU gene.

Topics: Adult; Aldehyde Oxidase; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Purine-Pyrimidine Metabolism, Inborn Errors; Sulfurtransferases; Uric Acid; Xanthine; Xanthine Dehydrogenase; Xanthine Oxidase

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a genetic disease of purine metabolism resulting in uric acid overproduction. Allopurinol, which inhibits the enzyme xanthine oxidase and reduces uric acid synthesis, is widely used for the treatment of gout and uric acid overproduction. The aim of the study was to analyze the long-term efficacy and safety of allopurinol in patients with HPRT deficiency. Nineteen patients (13 with Lesch-Nyhan syndrome and 6 with partial HPRT deficiency) were treated with allopurinol (mean dose, 6.4 mg/kg body weight per day; range, 3.7-9.7 mg/kg body weight per day) and followed up for at least 12 months (mean follow-up, 7.6 years). The efficacy of allopurinol was evaluated by serial measurement of purine metabolic parameters and renal function as well as by clinical manifestations. Safety was assessed by recording adverse events. Treatment with allopurinol normalized serum urate level in all patients and resulted in a mean reduction in serum urate of 47%. Allopurinol treatment was associated with a mean 74% reduction in urinary uric acid-to-creatinine ratio. In contrast, allopurinol treatment increased mean hypoxanthine and xanthine urinary excretion rates 5.4- and 9.5-fold, respectively, compared with baseline levels. The decrease in uric acid excretion in complete and partial HPRT-deficient patients was not accompanied by a stoichiometric substitution of hypoxanthine and xanthine excretion rates. Allopurinol-related biochemical changes were similar in patients with either complete or partial HPRT deficiency. Renal function remained stable or improved with treatment. Three patients had urolithiasis during allopurinol treatment. In 2 patients, xanthine stones were documented and they required allopurinol dose adjustments aimed at reducing excessive oxypurine excretion rates. No allopurinol hypersensitivity reactions occurred. Neurologic manifestations were not influenced by allopurinol therapy. In conclusion, allopurinol is efficacious and generally safe for the treatment of uric acid overproduction in patients with HPRT deficiencies. Xanthine lithiasis, developing as a consequence of allopurinol therapy, should be preventable by adjustment of allopurinol dose.

Topics: Adolescent; Adult; Allopurinol; Antimetabolites; Child; Child, Preschool; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Kidney; Lesch-Nyhan Syndrome; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Retrospective Studies; Treatment Outcome; Uric Acid

Allopurinol is used widely for the treatment of purine disorders such as gout, but efficacy and safety of allopurinol has not been analyzed systematically in an extensive series of patients with HPRT deficiency. From 1984 to 2004 we have diagnosed 30 patients with HPRT deficiency. Eighteen patients (12 with Lesch-Nyhan syndrome or complete HPRT deficiency, and 6 with partial HPRT deficiency) were treated with allopurinol (mean dose, 6.44 mg/Kg of weight per day) and followed-up for at least 12 months (mean follow-up 7,6 years per patient). Mean age at diagnosis was 7 years (range, 5 months to 35 years). Treatment with allopurinol was associated to a mean reduction of serum urate concentration of 50%, and was normalized in all patients. Mean urinary uric acid excretion was reduced by 75% from baseline values, and uric acid to creatinine ratio was close or under 1.0 in all patients. In contrast, hypoxanthine and xanthine urinary excretion rates increased by a mean of 6 and 10 times, respectively, compared to baseline levels. These modifications were similar in patients with complete or partial HPRT deficiency. In 2 patients xanthine stones were documented despite allopurinol dose adjustments to prevent markedly increased oxypurine excretion rates. Neurological manifestations did not appear to be influenced by allopurinol therapy. Allopurinol is a very efficacy and fairly safety drug for the treatment of uric acid overproduction in patients with complete and partial HPRT deficiency. Allopurinol was associated with xanthine lithiasis.

Topics: Adolescent; Adult; Allopurinol; Child; Child, Preschool; Follow-Up Studies; Humans; Hypoxanthine; Hypoxanthine Phosphoribosyltransferase; Infant; Lesch-Nyhan Syndrome; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Spain; Uric Acid; Xanthine

Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early. Compliance with allopurinol treatment and diet has been as important as early recognition. Hypertension has been rigorously controlled. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide?

Topics: Adolescent; Adult; Allopurinol; Child; Disease Progression; Family Health; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Nephritis, Hereditary; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Time Factors; United Kingdom

In most cases gout is the clinical manifestation of familial hyperuricemia. Pathogenesis of hyperuricemia, clinical manifestations, diagnosis and differential diagnosis of hyperuricemia and gout are described. Treatment of hyperuricemia consists of dietary measurements and administration of uric acid lowering drugs, such as allopurinol or uricosuric agents. Nonsteroidal antiinflammatory drugs, colchicine and glucocorticosteroids are the treatment of choice for the acute gout attack. Prophylaxis of acute uric acid nephropathy consists of hydration, urine alkalinization and administration of allopurinol or rasburicase. For treatment of acute uric acid nephropathy rasburicase is the drug of choice.

Topics: Allopurinol; Arthritis, Gouty; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Calculi; Prognosis; Purine-Pyrimidine Metabolism, Inborn Errors; Renal Insufficiency; Uricosuric Agents

A 43-year-old xanthinuric female was referred to our department because of hypouricemia. Routine laboratory data showed hypouricemia, a high level of plasma oxypurines, decreased urinary uric acid excretion, and increased urinary oxypurine excretion, with xanthine dehydrogenase activity in the duodenal mucosa below the limits of detection. In addition, allopurinol was not metabolized. From these findings, the patient was diagnosed with xanthinuria type II. To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency, a cDNA sequence encoding XDH/XO, aldehyde oxidase (AO), and molybdenum cofactor sulferase (MCS), as well as immunoblotting analysis for XDH/XO protein, obtained from duodenal mucosa samples were performed. The XDH/XO cDNA and AO cDNA sequences of the xanthinuric patient were consistent with previously reported ones, whereas the MCS cDNA sequence revealed a point mutation of G to C in nucleotide 466, which changed codon 156 from GCC (Ala) to CCC (Pro). In addition, the MCS genomic DNA sequence including the site of the mutation revealed the same, suggesting that the xanthinuric patient was homozygous for this mutation. Such findings have not been previously reported for patients with xanthinuria type II.

Topics: Adult; Aldehyde Oxidase; Allopurinol; Antimetabolites; DNA Primers; DNA, Complementary; Duodenum; Female; Humans; Hypoxanthine; Immunoblotting; Intestinal Mucosa; Point Mutation; Purine-Pyrimidine Metabolism, Inborn Errors; Sulfurtransferases; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase; Xanthines

A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previously reported in patients with classical xanthinuria type I.

Topics: Allopurinol; Humans; Hypoxanthine; Male; Middle Aged; Oxypurinol; Point Mutation; Purine-Pyrimidine Metabolism, Inborn Errors; Sequence Analysis, DNA; Xanthine; Xanthine Dehydrogenase

Measurement of purine and pyrimidine metabolites presents complex problems for separations currently performed by HPLC and thin-layer chromatography in clinical practice. We developed a novel capillary electrophoresis method for this purpose.. Separations were performed in 60 mmol/L borate-2-amino-2-methyl-1-propanol-80 mmol/L sodium dodecyl sulfate (pH 9.6) at 35 degrees C.. The conditions reported allowed separation of all diagnostic metabolites from major urinary constituents in an analysis time of 3 min and with a separation efficiency of 220 000 theoretical plates/m. The clinically important metabolites were detectable at concentrations of 0.85-4.28 micromol/L. The method was linear over the range 5-500 micromol/L (r >0.99). The within-run and intra- and interday imprecision (CV) was <5%. Characteristic abnormalities were detected in the electropherograms of urine samples from patients with purine and pyrimidine enzyme deficiencies. We provide the electrophoretic and spectral characteristics of many intermediates in purine and pyrimidine metabolism and describe common artifacts from medication and ultraviolet-absorbing compounds.. Capillary electrophoresis is a valuable screening tool in the detection of inborn errors of purine and pyrimidine metabolism.

Topics: Adenine Phosphoribosyltransferase; Adenosine Deaminase; Adenylosuccinate Lyase; Adolescent; Child; Child, Preschool; Dihydrouracil Dehydrogenase (NADP); Electrophoresis, Capillary; Female; Humans; Infant; Male; Oxidoreductases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Spectrophotometry, Ultraviolet; Xanthine Oxidase

Two brothers with classical xanthinuria who lacked xanthine dehydrogenase activity were encountered. Their hypouricemia was caused by underproduction of uric acid. In their duodenal mucosa, no xanthine dehydrogenase (oxidase) activity was detected. The patients had no symptoms except for duodenal ulcer in one case. The conversion of allopurinol to oxipurinol during an allopurinol loading test for determining the type of classical xanthinuria revealed that the patients had classical type 1 xanthinuria, because aldehyde oxidase activity was present. Furthermore, the allopurinol loading test was conducted to determine the optimal examination times and specimens required for this test.

Topics: Adult; Allopurinol; Humans; Male; Mutation; Oxypurinol; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Dehydrogenase; Xanthines

Topics: Adolescent; Adult; Allopurinol; Child; Child, Preschool; Female; Follow-Up Studies; Gout Suppressants; Humans; Kidney Diseases; Male; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Time Factors; Uric Acid

We studied purine metabolism in gouty patients from three categories: primary gout, familial juvenile hyperuricaemic nephropathy (FJHN) and partial HPRT deficiency.

Topics: Adolescent; Adult; Aged; Allopurinol; Benzbromarone; Creatinine; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Failure, Chronic; Male; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Child; Humans; Kidney Calculi; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adenine Nucleotides; Allopurinol; Child; Erythrocytes; Female; Guanine Nucleotides; Humans; Hypoxanthine; Hypoxanthines; Inosine; Male; NAD; Nuclear Family; Purine-Pyrimidine Metabolism, Inborn Errors; Reference Values; Ribonucleotides; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Uridine; Uridine Diphosphate Glucose; Xanthine; Xanthines

Topics: Allopurinol; Coenzymes; Female; Humans; Male; Metabolism, Inborn Errors; Metalloproteins; Molybdenum; Molybdenum Cofactors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine; Xanthine Dehydrogenase; Xanthines

A non-radiochemically sensitive method for the determination of xanthine oxidase (XO, EC 1.1. 3.22) activity is devised. We have enabled to detect the low activity of XO in human serum or peripheral lymphocyte lysates by the pretreatment of samples with activated charcoal, and by the employment of a sensitive high-performance liquid chromatography with electrochemical detection. This method was shown to be reliable and reproducible, and allowed us to evaluate XO activity in various clinical samples. XO activity in serum, but not in peripheral lymphocytes reflected the degree of liver damage. No relationship was found between serum XO activity and serum uric acid. No XO activity was detected in sera from patients with hereditary xanthinuria. These results suggested this method to be quite useful for rapid diagnosis of the patients with abnormal purine metabolism, especially in that with hereditary xanthinuria.

Topics: Adult; Chromatography, High Pressure Liquid; Female; Humans; Male; Methods; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine; Xanthine Oxidase; Xanthines

The presence of immunoreactive xanthine oxidase protein was proven in a xanthinuric patient, using a polyclonal antibody against xanthine oxidase. The antibody was raised against purified human liver xanthine oxidase in a rabbit. Double immunodiffusion method demonstrated the existence of an immunologically reactive xanthine oxidase which did not possess xanthine oxidase activity. In addition, urinary excretion of oxypurines in the patient and her family was investigated. The results indicated that a brother and a sister had xanthinuria.

Topics: Adult; Antibodies; Duodenum; Family; Female; Humans; Intestinal Mucosa; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

The antibody was raised against purified human liver xanthine oxidase in a rabbit. In a xanthinuric patient, the double immunodiffusion method demonstrated the existence of an immunologically reactive duodenal mucosa xanthine oxidase which did not possess xanthine oxidase activity. These results indicated that xanthine oxidase protein is abnormal in structure and/or amino acid sequence.

Topics: Female; Humans; Hypoxanthine; Hypoxanthines; Immunodiffusion; Liver; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Reference Values; Xanthine; Xanthine Oxidase; Xanthines

The lack of activity of the xanthine-oxidase conversion produces hypouricemia and hypocuria, with high urine elimination of xanthine and hypoxanthine. Due to the low solubility, it can result in urinary lithiasis. Two rare cases of xanthinuria caused by total lack of xanthine-oxidase are presented. A differential diagnosis of several congenital metabolic purine defects was carried out.

Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Female; Humans; Hypoxanthines; Male; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase; Xanthines

Genetic heterogeneity has been suggested in xanthinuria from the hitherto unexplained ability of some patients with this hereditary disorder to convert allopurinol to its active metabolite oxipurinol--an activity generally attributed to xanthine oxidase. This study provides evidence that the enzyme aldehyde oxidase is also deficient in xanthinuric patients not converting allopurinol to oxipurinol, whereas a xanthinuric patient with normal formation of oxipurinol had normal aldehyde oxidase activity. It is concluded that the enzyme aldehyde oxidase is the principal enzyme responsible for the formation of oxipurinol in man.

Topics: Adult; Aldehyde Oxidase; Aldehyde Oxidoreductases; Allopurinol; Humans; Male; Middle Aged; Oxypurinol; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrimidines; Xanthine Oxidase; Xanthines

Two brothers with hereditary xanthinuria (xanthine oxidase deficiency) and several members of their family were studied. In both subjects, plasma and urinary concentrations of uric acid were low whereas xanthine and hypoxanthine concentrations were markedly elevated. Xanthine oxidase activity was virtually absent in the patients' duodenal mucosa, a finding that established the diagnosis of hereditary xanthinuria. In their parents (obligate heterozygotes), the duodenal xanthine oxidase activity was about 50% of that in control subjects (father 9.3 and mother 12.8 mU/g tissue compared with 21.3 +/- 5.0 mU/g tissue, mean +/- SD). The residual xanthine oxidase from the parents exhibited normal kinetics with respect to hypoxanthine. The parents' urinary xanthine and hypoxanthine concentrations were significantly greater than those of control subjects, while their plasma concentrations of oxypurines were normal. Similar findings were observed in at least 6 other relatives, a finding that suggested that they were heterozygotes. This study suggests that obligate hereditary xanthinuria heterozygotes have only 50% of the xanthine oxidase activity of controls; this deficiency results in a partial metabolic blockage at this enzymatic step in heterozygotes.

Topics: Adult; Creatinine; Female; Heterozygote; Humans; Hypoxanthines; Kinetics; Male; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine; Xanthine Oxidase; Xanthines

The metabolism of pyrazinamide and allopurinol was studied in three xanthinuric patients from two families with hereditary xanthinuria to determine whether both substrates were oxidized only by xanthine oxidase or by other oxidases as well. One xanthinuric patient could neither metabolize pyrazinamide into 5-hydroxypyrazinamide nor allopurinol into oxypurinol. Two xanthinuric patients could metabolize both pyrazinamide into 5-hydroxypyrazinamide and allopurinol into oxypurinol but could not oxidize pyrazinoic acid to 5-hydroxypyrazinoic acid. These findings suggest that xanthinuria comprises at least two subgroups.

Topics: Adult; Allopurinol; Female; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Xanthines

A case of hereditary xanthinuria in a 68-year-old man with congestive heart failure and alcoholic liver disease is presented. Urolithiasis and muscular symptoms were absent, and the metabolic error was revealed by hypouricemia, hypouricosuria and excess of xanthine and hypoxanthine excretion in urine. Xanthine oxidase (EC 1.2.3.2) activity in liver tissue was absent, confirming the diagnosis of xanthinuria.

Topics: Aged; Biopsy, Needle; Heart Failure; Humans; Hypoxanthines; Liver; Liver Diseases, Alcoholic; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase; Xanthines

A female patient is described with combined deficiency of sulphite, zanthine and aldehyde oxidase. She presented at the age of four weeks with intractable seizures. Initially the diagnosis was suspected because of a very low serum urate level (23 mumol/1-1). This condition can be easily missed and it is proposed that measurement of serum urate be included in the metabolic assessment of neonates with unexplained seizures and developmental delay.

Topics: Aldehyde Oxidase; Aldehyde Oxidoreductases; Chromosome Aberrations; Chromosome Disorders; Coenzymes; Female; Genes, Recessive; Humans; Infant; Intellectual Disability; Metalloproteins; Molybdenum Cofactors; Oxidoreductases Acting on Sulfur Group Donors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase

We used a reversed-phase "high-performance" liquid-chromatographic system equipped with a multichannel ultraviolet spectrometric detector and a micro-computer for analyzing urine samples from patients with disorders of purine metabolism. This system recorded a series of absorption-spectrum data from a single chromatographic run and stored them for subsequent analysis. Because the retention times and ultraviolet absorption spectra of the eluates were recorded simultaneously, identification of peaks was easy and quite accurate for simultaneous quantification of orotidine, adenine, hypoxanthine, uric acid, xanthine, allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine), inosine, and 2,8-dihydroxyadenine--compounds extremely difficult or even impossible to quantify simultaneously with a conventional single-wavelength spectrometer. We used this method to investigate purine metabolites in urines from a patient with hereditary xanthinuria, three patients with 2,8-dihydroxyadenine urolithiasis, and a gouty subject taking allopurinol.

Topics: Adenine; Allopurinol; Chromatography, High Pressure Liquid; Humans; Hypoxanthine; Hypoxanthines; Inosine; Oxypurinol; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Spectrophotometry, Ultraviolet; Uric Acid; Uridine; Xanthine; Xanthines

We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

Topics: Adenine; Adenine Nucleotides; Adolescent; Adult; Female; Fructose; Guanosine; Humans; Hypoxanthine; Hypoxanthines; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthine; Xanthine Oxidase; Xanthines

Topics: Adenine Phosphoribosyltransferase; Glycogen Storage Disease Type I; Humans; Hypoxanthine Phosphoribosyltransferase; Immunologic Deficiency Syndromes; Japan; Mutation; Purine-Pyrimidine Metabolism, Inborn Errors; Ribose-Phosphate Pyrophosphokinase; Xanthine Oxidase

Topics: Female; Fetal Blood; Humans; Hypoxanthine; Hypoxanthines; Infant, Newborn; Pregnancy; Pregnancy Complications; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Genes, Recessive; Humans; Infant; Kidney Calculi; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine; Xanthine Oxidase; Xanthines

A case of combined deficiency of sulphite-oxidase and xanthine-oxidase with a defect of the molybdenum cofactor, which is vital to the activity of sulphite-, xanthine- and aldehyde-oxidase, is reported here. Seven cases of combined deficiencies have been described with regard to both clinical and laboratory findings. The clinical, laboratory and anatomo-pathological features and, in particular, the central nervous system lesions of the present case correspond exactly to those in the case described Rosenblum in which an isolated deficiency in sulphite-oxidase was present. As the cerebral alterations in the present case are comparable to those described in Rosenblum's case, they probably result from the defect in sulphite-oxidase activity.

Topics: Amino Acid Metabolism, Inborn Errors; Amino Acids, Sulfur; Brain; Child, Preschool; Coenzymes; Female; Humans; Liver; Metalloproteins; Microcephaly; Molybdenum; Molybdenum Cofactors; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Sulfates; Syndrome; Xanthine Oxidase; Xanthines

The purine metabolism of four cases with marked hypouricemia (serum uric acid concentration of less than 0.018 mmol/l) from three Japanese families was investigated. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine-nucleoside phosphorylase (EC 2.4.2.1) activities of the patients were within the normal ranges. Urinary hypoxanthine and xanthine concentrations were 0.096-0.397 mmol/l and 0.743-1.717 mmol/l, respectively. Xanthine oxidase (EC 1.2.3.2) activities in the jejunal mucosa of the two normal controls were 0.257 and 0.283 units/g protein, while those of three of the patients were extremely low and could not be determined. The findings of these biochemical features may indicate that the four patients have hereditary xanthinuria. In order to study the purine metabolism in the hypouricemic condition of this disorder, a single oral dose of allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) was administered in one case. The excretion pattern of allopurinol and oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine) in the urine of the patient was similar to that of a normal control male. These data suggest that some residual enzyme activity may be functioning in vivo, although the presence of xanthine oxidase could not be detected.

Topics: Adenosine Deaminase; Aged; Erythrocytes; Female; Humans; Male; Middle Aged; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Xanthine Oxidase; Xanthines

Topics: Adult; Female; Humans; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine; Xanthine Oxidase; Xanthines

Topics: Amniocentesis; Female; Humans; Infant; Infant, Newborn; Male; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Pregnancy; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase

Allopurinol-1-riboside, a major metabolite of allopurinol, is commonly thought to be directly synthesized by purine nucleoside phosphorylase (PNP) in vivo. As this enzyme is otherwise believed to function in vivo primarily in the direction of nucleoside breakdown, we have determined by high performance liquid chromatography and a conventional chromatographic method the urinary metabolites of allopurinol in a child deficient of PNP. In this patient approximately 40% of urinary allopurinol metabolites consisted of allopurinol-1-riboside, thus proving the possibility of indirect formation of allopurinol-1-riboside via allopurinol-1-ribotide in vivo, catalysed by hypoxanthine guanine phosphoribosyltransferase (HGPRT) and a phosphatase.

Topics: Allopurinol; Chromatography, Affinity; Chromatography, High Pressure Liquid; Guanine; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Male; Oxypurinol; Pentosyltransferases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides

Description a new case--the most precociously diagnosed in medical literature--of Xanthinuria, with the peculiarity of having débuted with cerebral haemorraging without lithiasis at any time. Metabolism of purines, characteristics of the disease in general and of the case concerned, and published cases are reviewed.

Topics: Cerebral Hemorrhage; Female; Hematuria; Humans; Hydrocephalus; Infant, Newborn; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Xanthine Oxidase; Xanthines

The clinical features and biological results in a second patient with a metabolic defect of the molybdenum cofactor are described. The first case was reported in 1978 by Duran et al. Their clinical description was similar with early encephalopathy and myoclonial and dislocation of the lens. Biologically, this condition is characterised by secondary hypo-uricemia and hypo-uricuria due to xanthine oxidase deficiency and by sulphituria, resulting from sulphite oxidase deficiency. These two enzymes have a common hepatic molybdenum cofactor, the structure and metabolism of which are only partially known.

Topics: Brain Diseases, Metabolic; Coenzymes; Consanguinity; Female; Humans; Infant; Metalloproteins; Molybdenum; Molybdenum Cofactors; Oxidoreductases; Oxidoreductases Acting on Sulfur Group Donors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase

Purine nucleotide degradation refers to a regulated series of reactions by which human purine ribonucleotides and deoxyribonucleotides are degraded to uric acid in humans. Two major types of disorders occur in this pathway. A block of degradation occurs with syndromes involving immune deficiency, myopathy or renal calculi. Increased degradation of nucleotides occurs with syndromes characterized by hyperuricemia and gout, renal calculi, anemia or acute hypoxia. Management of disorders of purine nucleotide degradation is dependent upon modifying the specific molecular pathology underlying each disease state.

Topics: Adenosine Deaminase; Adenosine Monophosphate; Adenosine Triphosphate; AMP Deaminase; Anemia; Animals; Deoxyribonucleotides; Female; Gout; Humans; Hypoxia; Male; Nucleotidases; Phosphorylation; Purine Nucleotides; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribonucleotides; Uric Acid; Urinary Calculi; Xanthine Oxidase

Topics: Cholinesterases; Humans; Male; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adenine; Adult; Allopurinol; Female; Humans; Kidney Calculi; Kidney Pelvis; Purine-Pyrimidine Metabolism, Inborn Errors; Urinary Calculi

Purine and pyrimidine metabolism have been investigated in the longest surviving case of hereditary orotic aciduria after 15 years of chronic uridine therapy. Several unusual features were recorded: 1. Although the uridine dosage (0.5 mmol/kg) was adequate to control an otherwise normal clinical status, orotic acid excretion was still excessive (in congruent 7 mmol/24 h). Urinary drug metabolites (uracil and uridine), however, accounted for less than 7% of the daily uridine dose, and no orotidine, or any abnormal pyrimidines or purines, were identified at any time. 2. Urinary uric acid excretion was high and plasma uric acid low, resulting in a clearance up to 4 times normal. This was attributed to the uricosuric effect of orotic acid. 3. In direct contrast to previous findings in gouty subjects and healthy male controls we noted: (i) no increase in plasma or urinary uric acid levels, or uric acid clearance, following the change from a low to a high nucleoprotein regime (normally up to two-fold); (ii) allopurinol reduced both urinary uric acid and total oxypurine levels by more than 50% on the low (normally unaffected) as well as the high (normally reduced 20-50%) nucleoprotein regime; (iii) a substantial (up to 70%) reduction in orotic acid excretion during allopurinol therapy (normally mild orotic aciduria), of similar magnitude and in parallel with the reduction in uric acid levels. Uric acid and orotic acid excretion were closely related throughout. These findings differ from those of a similar study of hereditary orotic aciduria and suggest there is competitive transport between exogenous (dietary) purines and pyrimidines, as well as an important interdependence between endogenous purine and pyrimidine metabolism, by mechanisms as yet undefined.

Topics: Adolescent; Allopurinol; Diet; Erythrocytes; Humans; Leukocytes; Male; Orotic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines

Topics: Adolescent; Arthritis; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Male; Nervous System Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Syndrome; Xanthine Oxidase

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Child, Preschool; Female; Humans; Kidney Calculi; Male; Pedigree; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Reference Values; Spectrophotometry

Urinary orotidine and orotic acid have been determined in a patient with purine nucleoside phosphorylase (PNP) deficiency under various dietary therapeutic conditions. For this purpose a new procedure for the analysis of both compounds has been developed, consisting of prefractionation with Dowex 1X8, followed by two HPLC steps on a micro Bondapak NH2 and a micro Bondapak C18 column. With this method normal as well as slightly elevated excretions of orotic acid have been found in our patient. No evidence was obtained for inhibition of OPRT by purine (deoxy)nucleosides as a cause of pyrimidine starvation. A significant increase of urinary orotidine was found after loading with allopurinol. For comparison excretory values in a patient with ornithine transcarbamylase deficiency and also in a patient with orotic aciduria type I are shown. The possible cause of the slight increase in urinary orotic acid in our patient has been discussed.

Topics: Allopurinol; Child; Child, Preschool; Chromatography, High Pressure Liquid; Deoxycytidine; Humans; Infant; Ornithine Carbamoyltransferase Deficiency Disease; Orotate Phosphoribosyltransferase; Orotic Acid; Orotidine-5'-Phosphate Decarboxylase; Pentosyltransferases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Respiratory Tract Infections; Uracil; Uridine

The Authors refer about three cases of asymptomatic xanthinuria pointed out after the discovery of very low serum uric acid levels (below 1 mg/100 ml). The above-mentioned cases come out from 137.194 evaluation of serum uric acid carried out in a period of about four years. The values of serum and urinary uric acid and those of total oxypurines in urine of same kinsmen of the three patients have been evaluated; all these values were in the normal range.

Topics: Adult; Aged; Female; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase; Xanthines

Hypouricaemia (blood level blow 2 mg/100 ml or 12 mumol/100 ml) is rarely observed, i.e., in less than 1% of hospitalized patients. Hypouricaemia can be induced by any of three mechanisms: a decrease in uric acid synthesis due to deficient xanthine oxydase (e.g., hereditary xanthinuria, severe liver disease, treatment with allopurinol); increased uricolysis due to drug therapy; increased urinary excretion of uric acid. This increased urinary excretion is due to abnormal uric acid transport in the proximal tubule. It is sometimes observed alone (primary hereditary anomaly of tubular uric acid transport, severe liver disease or neoplasia, drugs, or contrast media). It can also be observed in association with other proximal tubular anomalies, constituting a Fanconi syndrom. Among observations of hypouricaemia, 50% result from drug therapy and approximately 30% are secondary to liver diseases or neoplasia. It has no special clinical consequence. Nevertheless, the observation of hypouricaemia in a patient should indicate the possibility of drug intoxication or an underlying disease, in particular neoplasia. Measurement of uric acid clearance is a simple method of determining the mechanism responsible and of guiding diagnosis.

Topics: Allopurinol; Fanconi Syndrome; Humans; Liver Diseases; Neoplasms; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthines

Topics: Allopurinol; Dietary Proteins; Humans; Nucleoproteins; Orotic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines

Topics: Allopurinol; Child; Humans; Isoelectric Focusing; Mass Screening; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Time Factors

A method is presented for the two-dimensional thin-layer chromatographic screening of purines, pyrimidines and their nucleosides in the urine. Prior to chromatography, isolation of these substances from the urine is performed by anion-exchange column chromatography. Purines and pyramidines are quantitatively eluted with formic acid 0.01 M and 4 M respectively. The results of recovery and stability experiments are given. Normal excretory patterns are presented. Also results in patients with various diseases are shown: ornithine transcarbamylase deficiency, adenosine deaminase deficiency, purine nucleoside phosphorylase deficiency, adenine phosphoribosyltransferase deficiency, xanthine oxidase deficiency and hypoxanthine-guanine phosphoribosyltransferase deficiency. Finally the pattern of a patient on treatment with allopurinol is given.

Topics: Adenosine Deaminase; Allopurinol; ATP Phosphoribosyltransferase; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Chromatography, Thin Layer; Humans; Lesch-Nyhan Syndrome; Ornithine Carbamoyltransferase Deficiency Disease; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Xanthine Oxidase

Topics: Adolescent; Allopurinol; Child; Child, Preschool; Drug Therapy, Combination; Humans; Nephritis; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Uricosuric Agents

A chromatographic technique on anion exchange column was developed. It permets to determine unmetabolized pyrazinamide and three major metabolities: pyrazinoic acid, 5-hydroxypyrazinoic acid and an unidentified compound. In a xanthinuric patient only traces of 5-hydroxypyrazinoic acid were found 12 hours after 3 g pyrazinamide were given. These finding confirms that pyrazinoic acid is oxidised through the the action of xanthine oxidase. Both the clearances of hypoxanthine and of xanthine are as rapid as that of endogenous creatinine in a xanthinuric patient. But the effects of pyrazinamide are different on both purine bases. Urinary excretion of hypoxanthine is slightly but not significantly reduced while excretion of xanthine is decreased by about 75%. Evidence was demonstrated that pyrazinoic acid is likely the agent causing xanthine retention. These results suggest that the mechanisms of renal transport of xanthine and hypoxanthine are different.

Topics: Chromatography, Ion Exchange; Depression, Chemical; Humans; Hypoxanthines; Kidney; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Xanthine Oxidase; Xanthines

Xanthinuria, described in 1954 by Dent and Philpot, is a rare metabolic disorder, characterised by a deficiency in xanthine-oxidase, a key enzyme in the synthesis of uric acid. It results in hypouricaemia and hypouricuria, the urinary excretion of products of purine synthesis taking place in the form of uric acid precursors: hypoxanthine and xanthine. By virtue of the very slight solubility of xanthine, this xanthinuria may cause urinary lithiasis, in general occurring early. More often, however, the disease is asymptomatic and diagnosed following the chance discovery of hypouricaemia. We report 6 recent cases.

Topics: Adolescent; Adult; Child; Female; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Urinary Calculi; Xanthine Oxidase; Xanthines

A patient with hereditary erythrocyte pyrimidine 5' nucleotidase deficiency was studied to determine the mechanism of accumulation of erythrocyte pyrimidine nucleotides. Estimates of the rate of degradation of uridine nucleotides to diffusable products imply that the high levels found in these patients could not be sustained from the degradative pathways alone. Active synthesis of uridine nucleotides was found to occur in erythrocytes from both patient and control blood samples when either uridine or orotate was used as a substrate. The circulating levels of uridine in the blood are such that sufficient nucleotides to account for the high levels seen in these patients could accumulate in the erythrocytes from biosynthetic pathways alone, quite apart from the contribution from degradation of residual ribosomal RNA. This provides scope for new therapeutic approaches; treatment with allopurinol, however, was found to result in an increase, rather than a decrease, in erythrocyte pyrimidine nucleotides.

Topics: Adolescent; Allopurinol; Erythrocytes; Female; Humans; Male; Nucleotidases; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrimidines

Topics: Child; Diagnosis, Differential; Female; Humans; Hydronephrosis; Male; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Ureteral Calculi; Ureterostomy; Urography; Xanthine; Xanthine Oxidase

1. Abnormal amounts of adenine, 8-hydroxyadenine and 2,8-dihydroxyadenine are found in the urine of homozygotes for APRTase deficiency and are diagnostic of this condition. 2. The renal complication is due to the excessive amounts of 2,8-dihydroxyadenine excreted since it is removed by allopurinol which blocks 2,8-dihydroxyadenine formation. 3. Uric acid metabolism and the excretion of the other minor purine bases is normal, at least in childhood, in homozygotes for APRTase deficiency. 4. Patients with the defect appear to be very sensitive to dietary purine. At least some of the adenine metabolites may have a dietary origin.

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Child, Preschool; Diet; Humans; Male; Orotic Acid; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Child; Child, Preschool; Crystallization; Female; Heterozygote; Homozygote; Humans; Infant; Male; Pedigree; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Urinary Calculi

Topics: Adenine Phosphoribosyltransferase; Carbohydrate Metabolism; Feedback; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Lesch-Nyhan Syndrome; Models, Chemical; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Kidney Calculi; Male; Nephrosis; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Humans; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthines

Topics: Allopurinol; Gout; Humans; Muscles; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthines

Topics: Adult; Allopurinol; Diet; Humans; Hypoxanthines; Intestinal Mucosa; Male; Organophosphorus Compounds; Orotic Acid; Pentosephosphates; Phosphoric Acids; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Humans; Infant; Intellectual Disability; Male; Neurologic Manifestations; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid

Topics: Allopurinol; Biopsy; Diet; Humans; Jejunum; Liver; Male; Middle Aged; Orotic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrazoles; Pyrimidines; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Creatinine; Humans; Hypoxanthines; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrazoles; Pyrimidines; Sulfhydryl Compounds; Time Factors; Xanthines

Topics: Adenine; Allopurinol; Erythrocytes; Female; Gout; Guanine; Humans; Hypoxanthines; Lesch-Nyhan Syndrome; Male; Pentosephosphates; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrazoles; Pyrimidines; Sulfhydryl Compounds; Time Factors; Uric Acid; Xanthines

Topics: Allopurinol; Animals; Carbon Radioisotopes; Disease Models, Animal; Humans; Kidney; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Species Specificity; Swine; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Amino Acids; Aspirin; Autoanalysis; Creatinine; Glycosuria; Humans; Kidney Diseases; Neoplasms; Phosphates; Porphobilinogen; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Salicylates; Uric Acid; Xanthine Oxidase

Topics: Adenosine; Alkaline Phosphatase; Amidinotransferases; Amidohydrolases; Glomerular Filtration Rate; Glucosephosphate Dehydrogenase; Gout; Guanine Nucleotides; Humans; Hypoxanthines; Kinetics; Lesch-Nyhan Syndrome; Pentosephosphates; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Adenine; Adolescent; Adult; Aged; Allopurinol; Carbon Radioisotopes; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Female; Gout; Humans; Karyotyping; Male; Middle Aged; Pedigree; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribonucleosides; Uric Acid; Xanthines

Topics: Adult; Diagnosis, Differential; Gout; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adenine; Adolescent; Adult; Allopurinol; Athetosis; Australia; Child; Humans; Hypoxanthines; Intellectual Disability; Lesch-Nyhan Syndrome; Male; Phosphotransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Uric Acid; Xanthines

Topics: Adolescent; Adult; Aged; Child, Preschool; Female; Humans; Male; Middle Aged; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Urinary Calculi; Xanthine Oxidase; Xanthines

Topics: Gout; Humans; Lesch-Nyhan Syndrome; Purine-Pyrimidine Metabolism, Inborn Errors; Sex Factors; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Athetosis; Child, Preschool; Humans; Intellectual Disability; Lesch-Nyhan Syndrome; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Sex Factors; Syndrome

Topics: Adolescent; Allopurinol; Athetosis; Child, Preschool; Humans; Intellectual Disability; Lesch-Nyhan Syndrome; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Sex Chromosomes; Uric Acid

Topics: Allopurinol; Diphosphates; Guanine; Humans; Hypoxanthines; Nucleotides; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Transferases; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Athetosis; Brain; Child; Child, Preschool; Compulsive Behavior; Gout; Humans; Huntington Disease; Infant; Infant, Newborn; Intellectual Disability; Kidney Diseases; Liver; Prognosis; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Transferases; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Athetosis; Basal Ganglia; Diphosphates; Erythrocytes; Fibroblasts; Guanine; Humans; Hypoxanthines; Infant; Intellectual Disability; Lesch-Nyhan Syndrome; Liver; Pentosephosphates; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose; Self Mutilation; Transferases; Xanthines

Topics: Allopurinol; Androsterone; Colchicine; Gout; Gymnastics; Humans; Indomethacin; Kinins; Long-Term Care; Metabolism, Inborn Errors; Physical Education and Training; Purine-Pyrimidine Metabolism, Inborn Errors; Time Factors; Uric Acid; Uricosuric Agents

Topics: Adolescent; Allopurinol; Athetosis; Child; Humans; Hypoxanthines; Intellectual Disability; Lesch-Nyhan Syndrome; Male; Probenecid; Purine-Pyrimidine Metabolism, Inborn Errors; Pyelonephritis; Self Mutilation; Uric Acid; Urinary Calculi; Xanthines

Topics: Allopurinol; Brain Damage, Chronic; Child; Electroencephalography; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid

Topics: Animals; Carbon Isotopes; Cattle; Chromatography, Thin Layer; Colostrum; Female; Humans; Hypoxanthines; Milk; Pregnancy; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase

Topics: Adult; Biopsy; Female; Humans; Hypoxanthines; Intestinal Mucosa; Jejunum; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Spectrophotometry; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Depression, Chemical; Female; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines

Topics: Allopurinol; Depression, Chemical; Humans; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrimidines

Topics: Allopurinol; Athetosis; Child; Chorea; Compulsive Behavior; Humans; Intellectual Disability; Orotic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Self Mutilation; Uric Acid

Topics: Allopurinol; Diphosphates; Erythrocytes; Gout; Humans; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose; Transferases; Uric Acid

Topics: Biopsy; Humans; Hypoxanthines; Muscles; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adolescent; Adult; Age Factors; Allopurinol; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Male; Movement Disorders; Psychomotor Disorders; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Sex Factors; Transferases; Uric Acid

Topics: Allopurinol; Athetosis; Child; Child, Preschool; Chorea; Chromatography, Thin Layer; Densitometry; Humans; Hypoxanthines; Intellectual Disability; Male; Nucleosides; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Uric Acid; Xanthines

Topics: Adolescent; Adult; Alkaptonuria; Allopurinol; Amniotic Fluid; Athetosis; Carbohydrates; Chorea; Chromatography, Ion Exchange; Compulsive Behavior; Female; Gout; Humans; Hypertension; Infant; Infant, Newborn; Intellectual Disability; Male; Maple Syrup Urine Disease; Methods; Middle Aged; Nephritis; Nicotinic Acids; Phenols; Pregnancy; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Spectrophotometry; Sulfuric Acids; Ultraviolet Rays; Uric Acid; Xanthines

Topics: Humans; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Athetosis; Benzofurans; Brain; Child; Child, Preschool; Chorea; Compulsive Behavior; Erythrocytes; Female; Guanine; Humans; Hypoxanthines; Infant; Intellectual Disability; Japan; Kidney; Lesch-Nyhan Syndrome; Liver; Male; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Transferases; Uric Acid

Topics: Allopurinol; Gout; Humans; Purine-Pyrimidine Metabolism, Inborn Errors; Urate Oxidase; Uric Acid

Topics: Allopurinol; Athetosis; Azathioprine; Benzofurans; Child; Child, Preschool; Guanine; Humans; Hypoxanthines; Intellectual Disability; Japan; Ketones; Lesch-Nyhan Syndrome; Male; Paraplegia; Pentosyltransferases; Phenols; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Spasm; Uric Acid; Xanthines

Topics: Arthritis; Female; Humans; Middle Aged; Psoriasis; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adolescent; Adult; Allopurinol; Diet Therapy; Diet, Sodium-Restricted; Diuretics; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Male; Piperazines; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Adolescent; Allopurinol; Chromatography; Depression, Chemical; Erythrocytes; Fibroblasts; Humans; Leukocytes; Male; Psychomotor Disorders; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Transferases; Uric Acid; Urinary Bladder Calculi; Urinary Calculi; Xanthines

Topics: Adult; Birefringence; Calculi; Crystallography; Female; Humans; Hypoxanthines; Male; Microscopy, Polarization; Muscles; Muscular Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adenine; Allopurinol; Autistic Disorder; Carbon Isotopes; Child Behavior Disorders; Child, Preschool; Erythrocytes; Glucosyltransferases; Glycine; Gout; Guanine; Humans; Hypoxanthines; Intellectual Disability; Male; Mutism; Nucleotides; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthenes

1. A patient with congenital deficiency of xanthine oxidase (EC 1.2.3.2) (xanthinuria) excreted the xanthine isomer 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in his urine when the hypoxanthine isomer 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) was given by mouth. 2. The identity of the oxipurinol that the patient excreted was established by mass spectrometry. 3. The mass spectra and infrared spectra of allopurinol, oxipurinol, hypoxanthine and xanthine are compared. 4. A mechanism for the fragmentation of these compounds that occurs during their mass-spectrometric investigation is proposed. 5. A possible metabolic pathway for the oxidation of allopurinol to oxipurinol in the absence of xanthine oxidase is discussed.

Topics: Adult; Allopurinol; Humans; Hypoxanthines; Infrared Rays; Male; Models, Biological; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Spectrophotometry; Spectrum Analysis; Xanthine Oxidase; Xanthines

Topics: Animals; Carbon Isotopes; Cattle; Chemical Phenomena; Chemistry; Chromatography; Chromatography, Paper; Guanine; Humans; Liver; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Species Specificity; Spectrophotometry; Tritium; Xanthine Oxidase

Topics: Adult; Child; Humans; Kidney Calculi; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Athetosis; Child; Genes, Recessive; Guanine Nucleotides; Humans; Hypoxanthines; Intellectual Disability; Locomotion; Male; Neurologic Manifestations; Posture; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Sex Chromosomes; Speech Disorders; Transferases; Uric Acid

Topics: Allopurinol; Calculi; Drug Tolerance; Female; Gout; Guanine Nucleotides; Humans; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Transferases; Uric Acid; Uricosuric Agents; Xanthine Oxidase; Xanthines

The excretion of oxypurine metabolites in urine of patients with congenital hyperuricosuria exceeds, on a creatinine basis, that observed in any previously recognized metabolic anomaly. The ratio of hypoxanthine to xanthine is from 2:1 to 3:1 and results from increased hypoxanthine excretion, in contrast to other hyperuricosuric conditions where ratios of less than one have been reported. Administration of allopurinol (a xanthine-oxidase inhibitor) reduces the excretion of uric acid but results in an equivalent increase in xanthine and hypoxanthine. These features appear to be unique to congenital hyper-uricosuria.

Topics: Allopurinol; Child; Child, Preschool; Humans; Hypoxanthines; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthines

Topics: Allopurinol; Humans; Hypoxanthines; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthines

Topics: Adolescent; Allopurinol; Aminohydrolases; Athetosis; Brain; Central Nervous System Diseases; Cerebral Palsy; Chorea; Erythrocytes; Fibroblasts; Glucosyltransferases; Humans; Hypoxanthines; Intellectual Disability; Liver; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Spasm; Xanthines

Topics: Adenine; Carbon Isotopes; Chromatography; Guanine; Humans; Hypoxanthines; Male; Metabolism, Inborn Errors; Nucleotides; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Spectrophotometry; Uric Acid; Urine; Xanthine Oxidase; Xanthines

Topics: Blood; Blood Group Antigens; Carbon Isotopes; Catecholamines; Electrophoresis; Humans; Jejunum; Kidney; Liver; Metabolism; Pheochromocytoma; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Urine; Xanthine Oxidase; Xanthines