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 contribution of reduced purine salvage to the hyperuricemia associated with hypoxanthine-guanine phosphoribosyltransferase deficiency was measured by the intravenous administration of tracer doses of [8-(14)C]adenine to nine patients with normal enzyme activity, three patients with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, and six patients with the Lesch-Nyhan syndrome. The mean cumulative excretion of radioactivity 7 d after the adenine administration is 5.6+/-2.4, 12.9+/-0.9, and 22.3+/-4.7% of infused radioactivity for control subjects, partial hypoxanthine-guanine phosphoribosyltransferase-deficient subjects, and Lesch-Nyhan patients, respectively. To assess relative rates of nucleotide degradation in control and hypoxanthine-guanine phosphoribosyltransferase-deficient patients two separate studies were employed. With [8-(14)C]inosine administration, three control subjects excreted 3.7-8.5% and two enzyme-deficient patients excreted 26.5-48.0% of the injected radioactivity in 18 h. The capacity of the nucleotide catabolic pathway to accelerate in response to d-fructose was evaluated in control and enzyme-deficient patients. The normal metabolic response to intravenous fructose is a 7.5+/-4.2-mmol/g creatinine increase in total urinary purines during the 3-h after the infusion. The partial hypoxanthine-guanine phosphoribosyltransferase-deficient subjects and Lesch-Nyhan patients show increases of 18.6+/-10.8 and 17.3+/-11.8 mmol/g creatinine, respectively. Of the observed rise in purine exretion in control subjects, 40% occurs from inosine excretion and 32% occurs from oxypurine excretion. The rise in total purine excretion with Lesch-Nyhan syndrome is almost entirely accounted for by an elevated uric acid excretion. Increases in urine radioactivity after fructose infusion are distributed in those purines that are excreted in elevated quantities.The observations suggest that purine salvage is a major contributor to increased purine excretion and that the purine catabolic pathway responds differently to an increased substrate load in hypoxanthine-guanine phosphoribosyltransferase deficiency. The purine salvage pathway is normally an important mechanism for the reutilization of hypoxanthine in man.
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PMID:Overproduction of uric acid in hypoxanthine-guanine phosphoribosyltransferase deficiency. Contribution by impaired purine salvage. 44 34

A patient with clearly developed features of the full Lesch-Nyhan syndrome and complete lack of activity of hypoxynthine-phosphoribosyltransferase is described. The clinical picture was characterized by absence of spasticity, good control of autoaggression by behavior therapy, and no signs of renal insufficiency. After death, which was caused by a viral infection, pathological examination and a search for material immunologically cross-reacting with hypoxanthine-phosphoribosyltransferase were possible. In spite of increased serum urate levels and raised urinary uric acid excretion there were no signs of urate deposits or damage in the internal organs, including the kidneys. Crossreactive material was found in the liver, kidneys and spleen, a relatively rare finding in the full Lesch-Nyhan-syndrome. The absence of any specific pathological changes in the brain of this patient is in agreement with earlier reports.
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PMID:Pathological and immunological observations in a case of Lesch-Nyhan-syndrome. 49 64

The results are described of a behavioural programme designed to modify self-injurious behaviour of a child with Lesch-Nyhan syndrome. The treatment combined extinction of the injurious behaviour and reinforcement of alternative behaviour, and was successful in the controlled hospital environment. However, an attempt to teach the parents to continue the treatment at home failed. The results are discussed in terms of the possible relationship between organic and environmental factors in maintaining the injurious behaviour, and the importance of analysing both the behaviour itself and the factors (including familial) maintaining it. It is suggested that parents should be advised about management of behavioural problems at an early age.
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PMID:Problems in the behavioural treatment of self-injury in the Lesch-Nyhan syndrome. 52 Jul 17

The patient, H.Chr.B., was among the first reported with hyperuricemia and central nervous system symptoms. He has been found to have a variant of hypoxanthine guanine phosphoribosyl transferase (HPRT; E.C.2.4.2.8) distinct from the enzyme present in patients with the Lesch-Nyhan syndrome. The patient had chroeoathetosis, spasticity, dysarthric speech, and hyperuricemia. However, his intelligence was normal and he had no evidence of self-mutilation. There was no activity of HPRT in the lysates of erythrocytes and cultured fibroblasts when analyzed in the usual manner. Using a newly developed method for the study of purine metabolism in intact cultured cells, this patient was found to metabolize some 9% of 8-14C-hypoxanthine, and 90% of the isotope utilized was converted to adenine and guanine nucleotides. In contrast, cells from patients with the Lesch-Nyhan syndrome were virtually completely unable to convert hypoxanthine to nucleotides. The patient's fibroblasts were even more efficient in the metabolism of 8-14C-guanine, which was utilized to the extent of 27%, over 80% of which was converted to guanine and adenine nucleotides. The growth of the cultured fibroblasts of this patient was intermediate in media containing hypoxanthine aminopterin thymidine (HAT), whereas the growth of Lesch-Nyhan cells was inhibited and normal cells grew normally. Similarly in 8-azaguanine, 6-thioguanine, and 8-azahypoxanthine, the growth of the patient's cells was intermediate between normal and Lesch-Nyhan cells. These observations provide further evidence for genetic heterogeneity among patients with disorders in purine metabolism involving the HPRT gene. They document that this famous patient did not have the Lesch-Nyhan syndrome.
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PMID:Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome. 52 96

A now 45-year-old man with marked chronic tophous gout and recurrent nephrolithiasis has been followed for 12 years. First gouty symptoms appeared at age 18. Uric-acid reducing treatment freed the patient of symptoms, and bony and soft-tissue tophi in part regressed. The early onset and high urinary uric-acid excretion indicated increased uric-acid production. Decreased activity of the enzyme hypo-xanthine-guanine-phosphoribosyl transferase was demonstrated to be the cause of the hyperuricaemia, which led to an excessive purine synthesis. An almost complete loss of activity of this enzyme is the basis of the Lesch-Nyhan syndrome. In the described patient all of the neurological and behavioural disorders of the Lesch-Nyhan syndrome were absent. A pheochromocytoma was found to be the cause of malignant hypertension, which had been present for many years.
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PMID:[Juvenile gout with decreased activity of hypoxanthine-guanine-phosphoribosyl transferase and pheochromocytoma: partial persistence of tophi despite uric-acid reducing treatment for 12 years (author's transl)]. 66 12

The behavioural symptoms in a 10-year-old boy with Lesch-Nyhan syndrome were effectively ameliorated by the behavior therapy techniques of systematic desensitization and extinction. Therapy was undertaken in a highly controlled environment. The hypothesis that the self-destructive behaviours in this syndrome were voluntary and maintained through continuous reinforcement was confirmed. Characteristic biting and other maladaptive behaviours were extinguished. Over a period of time it was possible to remove all the physical restraints previously used to prevent the boy injuring himself. During treatment his anxiety, associated with phobic reaction to being unrestrained, was reduced by nitrous oxide. At 1 1/2 years follow-up the boy continues to be symptom-free. He attends a special class at school and is learning to walk with crutches. It is emphasied that a trained and experienced therapist and a controlled environment are essential for the success of this form of behaviour therapy, and the dangers inherent in this method of treatment are discussed.
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PMID:Behavior therapy for a child with Lesch-Nyhan syndrome. 66 67

Amniocentesis provides the prenatal diagnosis of chromosomal abnormalities and many biochemical disorders. Many of the biochemical assays are not routinely performed in many institutions. Those institutions utilizing autoradiographic studies routinely can make a diagnosis of biochemical disorders satisfactorily by utilizing a combination of bank cells, amniotic fluid cells and autoradiographic techniques. An example is given of this technique used in a patient with a family history of Lesch-Nyhan syndrome.
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PMID:Prenatal diagnosis of the Lesch-Nyhan syndrome. 72 99

A relationship between disordered metabolism of purines and the central nervous system has been established by the Lesch-Nyhan syndrome. In this disorder a virtually complete defect in the activity of HGPRT is associated with a syndrome of severe mental retardation, choreoathetoid cerebral palsy, and bizarre, self-mutilative behavior. In patients with partial defects in HGPRT, two have had symptoms that have been labeled spinocerebellar. Neither were appreciably ataxic, and the relationship between the symptoms and the enzyme defect remains to be established. Analysis of HGPRT in members of a large kindred with spinocerebellar degeneration revealed normal levels of the enzyme. These observations suggest that a relationship between the activity of HGPRT and clinical ataxia is remote.
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PMID:Ataxia and disorders of purine metabolism: defects in hypoxanthine guanine phosphoribosyl transferase and clinical ataxia. 73 27

Monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) activities have been measured in fibroblasts from nine healthy controls, three patients with maple syrup urine disease (MSUD) and six patients with Lesch-Nyhan syndrome. Both A and B types of MAO activity are found in these cell lines. In comparison to controls, the MAO activity is significantly reduced in cells from patients with Lesch-Nyhan syndrome. A different situation has been observed in the cell lines from MSUD patients: one showed a high MAO activity, another a significantly reduced activity, and the third was in the range of the normal controls. COMT activity is also present in these cells, but with a wide variation. No specific differences have been noted among the controls and the mutant cells.
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PMID:Monoamine oxidase and catechol-o-methyltransferase activity in cultured fibroblasts from patients with maple syrup urine disease, Lesch-Nyhan syndrome and healthy controls. 76 15

The metabolic consequence of hypoxanthine-guanine phosphoribosyltransferase deficiency, the accelerated rate of purine synthesis de novo, was utilized as a marker for the detection in cultured fibroblasts of heterozygosity for the Lesch-Nyhan syndrome. This marker was found to be very sensitive allowing the detection of mutant cells in nonselected mixed mutant: normal cell cultures even at low proportion of 1 to 10. Exposure of the mixed cultures to selection for the mutant cell with azaguanine increased the sensitivity of the test. Cultures from different biopsies, obtained from heterozygote females, were found to contain different proportions of the mutant cell, ranging from 10 to 84%.
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PMID:Increased de novo purine synthesis in cultured skin fibroblasts from heterozygotes for the Lesch-Nyhan syndrome. A sensitive marker for carrier detection. 76 26


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