Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Lesch-Nyhan syndrome is an x-linked defect of purine metabolism resulting in its classical form in major neurodevelopmental abnormality, hyperuricaemia, and hyperuricosuria. Uric acid calculi and crystalluria are common. Allopurinol is the main method of reducing serum and urinary uric acid levels, but results in xanthinuria and oxypurinoluria, both of which may cause crystal nephropathy and calculi. The variable ultrasonic appearances of multiple calculi and increased medullary echogenicity in four cases of long-standing treated disease and the nature of the renal disorder, which is at least partially iatrogenic, are described.
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PMID:Renal sonography in long standing Lesch-Nyhan syndrome. 199 70

An isocratic HPLC technique has been developed for the separation and measurement of urine and plasma oxypurines in a patient with xanthinuria. The case history and laboratory data are presented. Xanthine excretion was 172 mg/g creatinine and hypoxanthine was 45 mg/g creatinine. Uric acid was too small to be measured but uricase determination showed only 3 mg/24 hr. Serum oxypurine analysis showed hypoxanthine 0.87 mg/dl and xanthine 0.35 mg/dl. Uric acid was not seen in this patient's serum but could be readily measured in normal control subjects. The technique can also be used to separate nucleotides from purine bases, and we have demonstrated its application to the measurement of erythrocyte hypoxanthine guanine phosphoribosyl transferase and adenine phosphoribosyl transferase in a kindred associated with the Lesch-Nyhan syndrome.
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PMID:Separation and quantitation of oxypurines by isocratic high-pressure liquid chromatography: application to xanthinuria and the Lesch-Nyhan syndrome. 665 93

The contribution of enhanced purine salvage to the decreased total purine excretion associated with allopurinol therapy was measured by the intravenous administration of tracer doses of [8-(14)C] adenine to four patients with gout and normal purine salvage enzyme activity and four patients with the Lesch-Nyhan syndrome and absent purine salvage activity. The mean cumulative excretion of radioactivity 5 days after the adenine administration to patients not receiving and receiving (off and on) allopurinol therapy was 6.1% and 3.6% of infused radioactivity for gouty subjects and 15.9% and 20.8% for the Lesch-Nyhan patients. Urate pool size and urate turnover, as measured by pool labeling with [2-(14)C]uric acid, were substantially decreased in both groups of patients during allopurinol therapy. The intestinal loss of uric acid was estimated from these pool measurements on and off allopurinol. With a correction for this extrarenal purine loss, the mean cumulative excretions of radioactivity 5 days after adenine administration to patients off and on allopurinol therapy were 11.9% and 4.8% for the gouty subjects and 31.7% and 24.5% for the Lesch-Nyhan patients. In vitro studies demonstrated no alteration of the synthesis or degradation of adenine nucleotides by allopurinol in cultured human diploid fibroblasts. These observations suggest that enhanced purine salvage is an important component leading to decreased purine excretion during allopurinol therapy.
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PMID:Enhanced purine salvage during allopurinol therapy: an important pharmacologic property in humans. 729 39

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.
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PMID:[Inherited disorders of uric acid metabolism--classification, enzymatic- and DNA-diagnosis]. 897 10

The prevalence of urolithiasis has been increasing for the past few decades in industrialized nations. Uric acid calculi account for a significant percentage of urinary stones. Certain risk factors may be involved in the pathogenesis of uric acid nephrolithiasis, including hyperuricosuria, low urinary volume, and persistently low urinary pH. Patients with medical conditions that promote profound hyperuricosuria are at high risk of developing uric acid calculi. These conditions include chronic diarrheal states; myeloproliferative disorders; insulin resistance, including diabetes mellitus; and monogenic metabolic disorders, such as Lesch-Nyhan syndrome. Computed tomography can provide a definitive diagnosis. Except in cases in which there is severe obstruction, progressive azotemia, serious infection, or unremitting pain, the initial treatment of patients with uric acid nephrolithiasis should be medical dissolution therapy because this approach is successful in the majority of cases. A thorough review of the epidemiology and pathophysiology of uric acid nephrolithiasis is crucial for the diagnosis, treatment, and prevention of stones in patients with this condition.
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PMID:Uric Acid nephrolithiasis: recent progress and future directions. 1739 68

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15-18 weeks' gestation, or chorionic villus cells obtained at about 10-12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments.
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PMID:Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. 1806 74