pyrophosphate and Metabolism--Inborn-Errors

Topics: Acidosis, Renal Tubular; Bacterial Infections; Citrates; Crystallization; Cystinuria; Diphosphates; Female; Gastrointestinal Diseases; Humans; Hypercalcemia; Hyperparathyroidism; Magnesium; Male; Metabolism, Inborn Errors; Mucoproteins; Oxalates; Quaternary Ammonium Compounds; Sarcoidosis; Solubility; Uric Acid; Urinary Calculi; Vitamin D; Xanthine Oxidase

Topics: Bone and Bones; Bone Development; Bone Diseases; Calcitonin; Calcium Metabolism Disorders; Child, Preschool; Densitometry; Diphosphates; Homeostasis; Humans; Hyperparathyroidism; Hypophosphatasia; Hypophosphatemia, Familial; Infant; Metabolism, Inborn Errors; Microradiography; Osteogenesis Imperfecta; Osteoporosis; Parathyroid Glands; Parathyroid Hormone; Phosphorus Metabolism Disorders; Pseudohypoparathyroidism; Rickets; Vitamin D

A patient with hypokalemic metabolic alkalosis, hypophosphatemia, and hypomagnesemia/hypocalcemia is described. Electrocardiography demonstrated the pattern of acute anterior myocardial infarction. Further evaluation revealed that the patient had not actually had the acute myocardial infarction and that the electrocardiographic change was a mere simulation. The possible role of hypomagnesemia in the pathogenesis of the electrocardiographic change and the interrelation between the metabolic disturbances noted are discussed.

Topics: Alkalosis; Diagnosis, Differential; Diphosphates; Electrocardiography; Humans; Hypocalcemia; Hypokalemia; Hypophosphatemia, Familial; Magnesium; Male; Metabolism, Inborn Errors; Middle Aged; Myocardial Infarction; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Child, Preschool; Diphosphates; Enzyme Activation; Fibroblasts; Freezing; Guanine; Humans; Hypoxanthines; Lesch-Nyhan Syndrome; Male; Metabolism, Inborn Errors; Middle Aged; Mutation; Pentosyltransferases

A family is reported in which each of two sisters has a son with no detectable hypoxanthine phosphoribosyltransferase (HPRT) (EC 2. 4. 2. 8) in his erythrocytes, a finding considered pathognomonic of Lesch-Nyhan disease. However, neither has the stigmata of the disease. One boy is neurologically normal, and the other is moderately retarded. There was only a slight increase in urinary uric acid, but the amounts of hypoxanthine and xanthine, and their ratios, were similar to those found in Lesch-Nyhan disease, strongly indicating that excesses of these last two oxypurines are not responsible for the symptomatology in that disease. In contrast to the nondetectable HPRT activity in the red blood cells, leukocyte lysates from the two boys have 10-15% of normal activity, possibly reflecting continuing synthesis of an unstable enzyme. This hypothesis is supported by the demonstration that at 4 degrees C HPRT activity was rapidly lost in the propositus while the activity increased in control subjects. The mother's cells were intermediate between the two. The intact and disrupted leukocytes of the hemizygote, in the absence of added phosphoribosyl converted as much hypoxanthine to inosinate as the normal cell, and appropriate tests indicated that under these circumstances enzyme concentration is not rate limiting whereas the concentration of the cosubstrate, phosphoribosyl pyrophosphate, is. The capacity for normal function in the intact mutant cell is more representative of in vivo conditions than the lysate, which may explain the important modification of clinical symptomatology, the relatively mild hyperuricosuria, and the presence of mosaicism in the circulating blood cells of the heterozygotes. A similar explanation may apply to other genetic diseases in which incomplete but severe enzyme deficiencies are found in clinically normal individuals. An associated deficiency in glucose-6-phosphate dehydrogenase in this family permitted confirmation of previous observations on linkage with hypoxanthine phosphoribosyltransferase.

Topics: Adolescent; Carbon Isotopes; Diphosphates; Epilepsy, Tonic-Clonic; Erythrocytes; Genotype; Glucosephosphate Dehydrogenase Deficiency; Heterozygote; Humans; Hypoxanthines; Inosine Nucleotides; Intellectual Disability; Lesch-Nyhan Syndrome; Leukocytes; Male; Metabolism, Inborn Errors; Mosaicism; Pedigree; Pentosyltransferases; Temperature; Uric Acid; Xanthines

Topics: Adult; Allopurinol; Child; Child, Preschool; Diphosphates; Erythrocytes; Female; Gout; Humans; Infant; Kidney Calculi; Male; Metabolism, Inborn Errors; Phosphotransferases; Purines; Uric Acid

An isotope dilution method, using (32)P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP(1)) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP(1) was +/-13%. There were no differences in plasma PP(1) between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (+/-SE) of PP(1) in the plasma of 73 men and women was 3.50 +/-0.11 mumoles/liter (0.217 +/-0.007 mug P/ml) and the normal range (99% limits) was 1.19-5.65 mumoles/liter (0.074-0.350 mug P/ml). It has been suggested that PP(1) may be important in calcium metabolism because PP(1) can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP(1) was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, "acute" osteoporosis, and primary hyperparathyroidism. Plasma PP(1) was invariably raised in hypophosphatasia. The excess of PP(1) in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Bone Diseases; Calcium; Chromatography, Ion Exchange; Chromatography, Paper; Dialysis; Diphosphates; Humans; Hypophosphatasia; Metabolism, Inborn Errors; Osteogenesis Imperfecta; Osteopetrosis; Phosphoric Monoester Hydrolases; Phosphorus Isotopes; Pyrophosphatases; Radioisotope Dilution Technique

Topics: Alkaline Phosphatase; Amino Alcohols; Bone Diseases; Calcification, Physiologic; Calcium; Child, Preschool; Diphosphates; Female; Humans; Metabolism, Inborn Errors; Phosphates; Phosphoric Monoester Hydrolases

Topics: Alkaline Phosphatase; Calcification, Physiologic; Calcinosis; Chromatography; Diphosphates; Fluids and Secretions; Hypophosphatasia; Metabolism, Inborn Errors; Phosphorus Isotopes; Urine