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)

Lesch-Nyhan syndrome is a rare X-linked disease characterized by over-production of uric acid and a central nervous system (CNS) disorder consisting of mental retardation, spasticity, choreoathetosis, and a compulsive form of self-mutilation. A deficiency in hypoxanthine-guanine phosphoribosyl transferase (HPRT) provides the underlying metabolic basis for this disease. A 12 month-old male baby who had orange crystals over the diapers since he was 3 months old was brought to our hospital due to developmental delay. Mental retardation and athetosis were also noted. Chemical analysis revealed hyperuricemia (uric acid 8.6 mg/dl). Urine routine showed microscopic hematuria and uric acid crystals. The activity of HPRT in erythrocyte lysates of parents were both within normal limits, but that of the patient was very low (0.0547 nm/min/mg protein, < 0.05% of control). His younger brother was born 2 months after this disorder diagnosed in this patient. The younger brother was noted to have uric acid crystals over the diapers when he was 40 days old and hyperuricemia (10.6 mg/dl) showed up later. He was also a case of Lesch-Nyhan syndrome since the activity of HPRT in erythrocyte lysates was also low (0.0327 nmol/min/mg protein, < 0.05% of control). Further studies, including carrier detection and deoxyribonucleic acid (DNA) analysis, could be helpful for genetic counseling. This syndrome is rare among Chinese, and this may be due to underdiagnosis.
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PMID:Lesch-Nyhan Syndrome: report on two brothers. 783 90

Lesch-Nyhan syndrome is a rare anomaly consisting of a deficiency in the production of hypoxanthine phosphoribosyltransferase that leads to the overproduction of purine and the accumulation of uric acid. Major manifestations include mental retardation and self-destructive behavior resulting in self-mutilation through biting and scratching. Because no medical treatment exists to alleviate the symptoms of self-mutilation, direct dental intervention is the only way these behaviors can be affected. A unique case of this type involving two male identical twins is reported.
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PMID:Lesch-Nyhan syndrome. A case report. 797 May 91

Lesch-Nyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and factitious oral lesions, which cause immense difficulties in its management. A case of an 11-year-old boy, the elder of two siblings with this condition, who had severe self-inflicted injuries to oral and perioral tissues is presented highlighting the different treatment modalities considered. A tailor-made lipguard proved to provide the best cosmetic result short term.
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PMID:Lesch-Nyhan syndrome and the lower lip guard. 823 22

Fragile X syndrome is the most common form of inherited mental retardation in man. The disease is associated with expansion in the number of tandem CGG trinucleotide repeats in the 5' untranslated region of the human FMR1 gene. Transmitting males, individuals who are unaffected carriers of the disease, show a moderate increase in the number of repeat units, while fully penetrant males show a major expansion in repeat number. Major expansion of the repeat in affected males is correlated with methylation of certain restriction enzyme recognition sites in the 5' CpG island containing the trinucleotide repeat in these patients. Phenotypic expression of the mutation appears to be due to transcriptional silencing of the FMR1 gene. We now report direct high resolution methylation analysis of the trinucleotide repeat and its flanking regions using ligation-mediated PCR genomic sequencing. We find the cytosine residue of all CpG dinucleotides examined within and surrounding the FMR1 trinucleotide repeat to be unmethylated in the DNA of normal male leukocytes and transmitting male lymphoblasts; these same cytosines are methylated in affected male lymphoblasts, in a somatic cell hybrid containing a fragile X chromosome from an affected male, and in a somatic cell hybrid containing a normal inactive X chromosome. The methylation pattern of the FMR1 5' CpG island in affected patients as determined by genomic sequencing is remarkably similar to that seen for the X-linked human phosphoglycerate kinase and hypoxanthine phosphoribosyltransferase gene 5' CpG islands on the inactive human X chromosome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome. 826 19

The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan syndrome and the evaluation of novel therapies.
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PMID:Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. 848 79

The Lesch-Nyhan syndrome results from a complete or virtually complete deficiency of the purine salvage enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT). The disease is characterized by hyperuricemia, choreoathetosis, spasticity, compulsive self-mutilation, and mental retardation. Patients with a partial deficiency of HPRT are spared most of the neurological disorder of Lesch-Nyhan syndrome. The specific relationship between HPRT deficiency and the neurological dysfunction in the Lesch-Nyhan syndrome is not known, at present. The genetic lesion which result in HPRT deficiency are heterogeneous. About 90 different mutations were found in over 110 families. The DNA-based mutation detection technique can be used for the diagnosis of affected males and for the determination of carrier status of asymptomatic females. This technique is also applicable for the prenatal diagnosis for Lesch-Nyhan syndrome. Transgenic mice, deficient in HPRT activity, have been obtained but they do not show any neurological dysfunction. After administration of 9-ethyladenine, however, they showed the self-injury behavior.
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PMID:[Complete and partial deficiency of HPRT]. 897 12

Lesch-Nyhan syndrome is a hereditary disorder of purine metabolism causing overproduction of uric acid and neurological problems including spasticity, choreoathetosis, mental retardation, and compulsive self-mutilation. The syndrome is caused by a defect in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), which converts guanine and hypoxanthine to the nucleotides GMP and IMP. There is evidence that the neurological problems are due to an adverse effect of the HPRT deficiency on the survival and/or development of dopaminergic neurons, specifically. Here we report that HPRT-deficient PC12 mutants that have a normal or near normal dopamine content (55-97% of that of wild-type cells) fail to undergo neuronal differentiation induced by nerve growth factor (NGF) when the de novo pathway of purine synthesis is partially inhibited. However, nerve growth factor-induced differentiation is near normal under these conditions in PC12 HPRT-deficient mutants containing much lower dopamine levels (<8% of that of wild type cells), indicating a neurotoxic effect of the endogenous dopamine in the mutants. The degree of inhibition of the de novo pathway of purine synthesis was the same in both classes of HPRT-deficient mutants. Expression of BCl-2 in a PC12 mutant that has a normal dopamine content allowed partial NGF-induced differentiation suggesting that the apoptotic pathway might be involved in the failure of differentiation when the de novo pathway of purine synthesis is partially inhibited.
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PMID:Impaired differentiation of HPRT-deficient dopaminergic neurons: a possible mechanism underlying neuronal dysfunction in Lesch-Nyhan syndrome. 967 Sep 94

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.
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PMID:Screen for MAOA mutations in target human groups. 1005 Sep 62

With few exceptions (e.g., Lesch-Nyhan syndrome), the specific nature of self-injury in relation to identified genetic syndromes associated with mental retardation is poorly understood. In the present study we surveyed the families of 62 persons with Prader-Willi syndrome to determine the prevalence, topographies, and specific body locations of self-injurious behavior. Self-injury was reported for 81% of the participants. Skin-picking was the most prevalent form, with the front of the legs and head being disproportionately targeted as preferred self-injury body sites. Individuals with the 15q11-q13 deletion injured significantly more body sites than did individuals with maternal disomy 15. Results are discussed in relation to previous self-injury body site findings and implications for the relevance of syndrome-specific behavioral phenotypes.
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PMID:Self-injurious behavior and Prader-Willi syndrome: behavioral forms and body locations. 1034 67

Lesch-Nyhan syndrome (LN) is a severe X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine phosphoribosyl transferase (HRT). Clinical features displayed by affected boys are particularly severe and disturbing and include hyperuricaemia, Characteristic neurological features including self-mutilation, choreothetosis, spasticity and mental retardation. A couple with a boy diagnosed with LN and a history of pregnancy termination was referred to the Hammersmith Hospital. Their affected son was born in 1982 after an uncomplicated pregnancy and vaginal delivery. Eight subsequent pregnancies had been unsuccessful. There were five therapeutic terminations and three spontaneous abortions, one at least directly caused by the sampling procedure during amniocentesis. From 1989 to 1991 two unsuccessful preimplantation genetic diagnosis (PGD) cycles by sexing were performed by DNA amplification. The mutation was characterized and a nested PCR protocol was designed which allowed the efficient amplification of the affected loci followed by the detection of the mutant allele by restriction digestion. Three PGD cycles were performed using this specific diagnostic test before a successful pregnancy was achieved resulting in the birth of a healthy unaffected baby girl.
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PMID:Successful preimplantation genetic diagnosis for sex Link Lesch--Nyhan Syndrome using specific diagnosis. 1069 59


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