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 alterations of three erythrocyte purine enzymes were studied in 12 patients with diseases associated with reticulocytosis, two patients with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, seven patients with severe megaloblastic anemia, and 14 normal subjects. The specific activity of adenine phosphoribosyltransferase was positively correlated (r = 0.81) with the reticulocyte percentate in ten patients with a normal hypoxanthine-guanine phosphoribosyltransferase. Two apparent types of alterations of this enzyme were distinguished: (1) increased specific activity with a normal half life as in megaloblastic anemia, and (2) a prolonged half life with or without an elevation of specific activity as in the deficiency of hypoxanthine-guanine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase were increased in megaloblastic anemia, but were not correlated with the reticulocyte percentage and did not have a consistent change in the half life in the other disorders studied. The data show that acquired disorders associated with reticulocytosis may cause an elevation of the specific activity of purine enzymes in peripheral circulating erythrocytes. Therefore, these factors must be carefully considered in the interpretation of an elevated level of enzyme activity.
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PMID:Acquired increases of human erythrocyte purine enzymes. 17 42

The possible factors in the pathogenesis of the brain damage and megaloblastic anaemia in the Lesch-Nyhan syndrome are discussed. Disordered growth and function appear to be limited to the brain, bone marrow and general body stature, yet the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8, HGPRT), although present in variable amounts in different tissues, is ubiquitous, a fact which suggests that other factors than HGPRT deficiency alone determine the pattern of tissue damage. Recent evidence suggests that the specific tissue damage in the Lesch-Nyhan syndrome is due to lack of NGPRT in tissues with relatively reduced purine de novo capability and a greater dependence on purine salvage pathways at certain stages in their development for their supply of purine ribonucleotides. This evidence is presented together with possible mitigating factors operating in the bone marrow.
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PMID:Factors in the pathogenesis of the brain damage and anaemia in the Lesch-Nyhan syndrome. 24 94

The incorporation of [15N]delta-aminolaevulinic acid and [15N glycine into haemoglobin haem and early labelled bilirubin was measured in subjects with various haematological disorders. The clearance of [14C bilirubin was used to measure bilirubin production rate, and the magnitude of the various sources of bilirubin production and the percentage ineffective erythropoiesis were calculated. Ineffective erythropoiesis was found to be a major factor in the production of the anaemia in patients with the following disorders: megaloblastic anaemia associated with the Lesch-Nyhan syndrome, thalassaemia intermedia, sideroblastic anaemia, and the anaemia of chronic disorders. In three patients with iron-deficiency anaemia ineffective erythropoiesis was increased, but was of minor importance in the production of the anaemia, while in two patients with aplastic anaemia and one with macrocytosis of alcoholism there was no increase in ineffective erythropoiesis.
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PMID:Quantitation of ineffective erythropoiesis from the incorporation of [15N] delta-aminolaevulinic acid and [15N] glycin into early labelled bilirubin. II. Anaemic patients. 95 67

A 12-year-old boy was referred because of abdominal pain, gross hematuria, and passage of stones. Further evaluation showed growth delay, low average range of intellectual functioning, and a speech articulation disorder. No signs of self-mutilation or self-injurious behavior were present. He had hyperuricemia, hyperuricosuria, uric acid crystalluria, uric acid calculi, macrocytosis, megaloblastic bone marrow changes, and mild anemia. Hypoxanthine phosphoribosyltransferase (HPRT) enzyme activity was reduced to approximately 26% of normal. Polymerase chain reaction-single strand conformational polymorphism analysis of the HPRT gene in DNA isolated from the patient's blood lymphocytes revealed a single nucleotide substitution at codon 200 in exon 8. The base change was a guanine to cytosine transversion, resulting in the conservative amino acid substitution of threonine in place of arginine. To our knowledge, this mutation has not previously been reported.
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PMID:A new point mutation in a hypoxanthine phosphoribosyltransferase-deficient patient. 932 99

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