Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sex-linked familial neurological disease consisting of cerebral palsy, mental retardation, choreoathetosis, and compulsive aggressive behavior is associated with a loss of an enzyme that participates in purine metabolism, namely, hypoxanthine-guanine phosphoribosyltransferase. The production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis. This is the first example of a relation between a specific enzyme defect and abnormal compulsive behavior. It is also the first enzyme defect in purine metabolism demonstrated in a neurological disease.
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PMID:Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. 602 Feb 92

Athetotic cerebral palsy was diagnosed in a 6-month-old boy with no history of perinatal trauma. Lesch-Nyhan syndrome (i.e., complete deficiency of hypoxanthine-guanine phosphoribosyltransferase [HGPRT] ) was diagnosed only when the boy began biting his lower lip at the age of 10 years. It is suggested, on the basis of this case and others like it in the literature, that the delayed onset or absence of self-mutilation in patients with Lesch-Nyhan syndrome may be more common than has been previously suspected. In all males said to have cerebral palsy, HGPRT deficiency must be ruled out, preferably by measuring the ratio of uric acid to creatinine in a random urine specimen.
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PMID:Differential diagnosis of cerebral palsy: Lesch-Nyhan syndrome without self-mutilation. 672 97

Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder resulting from a deficiency of the metabolic enzyme hypozanthine-guanine phosphoribosyltransferase (HPRT). This syndrome presents with abnormal metabolic and neurological manifestations including hyperuricemia, mental retardation*, spastic cerebral palsy (CP), dystonia, and self-mutilation. The mechanism behind the severe self-mutilating behavior exhibited by patients with LNS is unknown and remains one of the greatest obstacles in providing care to these patients. This report describes a 10-year-old male child with confirmed LNS who was treated for self-mutilation of his hands, tongue, and lips with repeated botulinum toxin A (BTX-A) injections into the bilateral masseters. Our findings suggest that treatment with BTX-A affects both the central and peripheral nervous systems, resulting in reduced self-abusive behavior in this patient.
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PMID:Botulinum toxin as a novel treatment for self-mutilation in Lesch-Nyhan syndrome. 1613 73

Lesch-Nyhan disease (LND) is a rare X-linked recessive genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. The classic clinical condition is characterized by cognitive impairment, hypotonia at rest, choreoathetosis, hyperuricaemia and the hallmark symptom of severe and involuntary self-mutilation. We describe a man with LND who was initially thought to have suffered from a dyskinetic cerebral palsy after an uncomplicated inguinal herniorrhaphy under general anaesthesia at 5 1/2 months of age. In the absence of overt self-injurious behaviour, the diagnosis was not considered for nearly two decades. The diagnosis of LND was established at 20 years of age through clinical review, biochemical examinations and molecular analysis. HPRT haemolysate activity was 7.6% of the normal control, suggesting that he had a milder variant of the disease. Mutation analysis of the HPRT gene revealed a novel missense mutation, c.449T > G in exon 6 (p.V150G). Cascade testing of family members revealed that the mother was heterozygous for the mutation but two siblings (a brother and a sister) did not carry the sequence mutation. Whether the onset of neurological abnormalities in this particular case can be attributed to the general anaesthesia is discussed.
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PMID:Lesch-Nyhan disease in a 20-year- old man incorrectly described as developing 'cerebral palsy' after general anaesthesia in infancy. 1682 47

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 enzyme deficiency. The complete deficiency causes Lesch-Nyhan syndrome (LNS). Partial HPRT-deficient patients can show a variable degree of neurological manifestations. Both diseases have been associated with mutations in the HPRT1 gene. Documented mutations in HPRT deficiency show a high degree of heterogeneity in type and location within the gene. In fact, more than 300 disease-associated mutations have been described. Splice mutations accounts for more that 16% of HPRT mutations and in most cases cause a complete LNS phenotype. A 16 year-old boy consulted to La Paz University Hospital because of hyperuricemia (9.4 mg/dL). At age one year he was given a diagnosis of dystonic cerebral palsy. Although he usually employs a wheelchair, under certain circumstances, he is able to stand up and walk by himself. He has never showed self injurious behavior. This patient presented a splice mutation (NM_000194.2: c.552 -2 A > G) causing exon 5 exclusion. An exon-5 specific PCR was designed, and a minor amount of normally spliced HPRT mRNA was found. Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients. No correlation was found between the percentage of the normally spliced HPRT mRNA and the phenotype. We conclude that the partial HPRT deficient phenotype of this patient can not be explained by the finding of a minor amount of normally splice HPRT mRNA. It is possible that the amount of normally splice mRNA vary among different tissues.
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PMID:Partial HPRT deficiency phenotype and incomplete splicing mutation. 2054 10