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 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 rare, x-linked, recessive disorder of purine metabolism resulting in hyperuricemia, spasticity, choreoathetosis, dystonia, self-injurious behavior, and aggression, without significant cognitive impairment. Anesthetic management of inpatients who demonstrate classic manifestations of Lesch-Nyhan syndrome and require surgical interventions have been described. There are no guidelines in the literature addressing the anesthetic management of the outpatient with Lesch-Nyhan syndrome. Specifically, sudden, unexplained death, abnormalities in respiration, apnea, severe bradycardia, and an increased incidence of vomiting and chronic pulmonary aspiration may preclude this patient population from receiving anesthesia for outpatient procedures. General anesthesia with spontaneous ventilation was performed for diagnostic, radiographic imaging in 11 outpatients with Lesch-Nyhan syndrome using intravenous propofol. A bolus dose of 1.5 to 2.0 mg/kg propofol was followed by maintenance doses of 60 to 160 mcg/kg/min. Results during and following sedation indicated end-tidal carbon dioxide ranges between 34 mmHg and 59 mmHg. Respiratory rates were never below 10 breaths/min and no partial/complete airway obstruction or labored breathing was clinically evident. Hemodynamics were within 30% of presedation values. No patient demonstrated nausea, vomiting, or pulmonary aspiration. Baseline neuropsychologic status was achieved following sedation, and patients were discharged from the hospital 35 to 90 minutes after sedation was completed. Potential risks and benefits of using propofol in this patient population are discussed.
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PMID:Use of propofol anesthesia during outpatient radiographic imaging studies in patients with Lesch-Nyhan syndrome. 905 48

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

Lesch-Nyhan syndrome (LNS) is a rare disorder of metabolism caused by a defective gene on the X chromosome. It is typically characterized by choreoathetosis, hypertonia, hyperreflexia, and self-mutilation. The present study is a 4-year follow-up investigation of the cognitive status of six subjects with a mean age of 17 years 10 months (range 14 years 9 months to 23 years). The Stanford-Binet Intelligence Scale: IV was used. Each of the four domains assessed by this battery (verbal reasoning, abstract/visual reasoning, quantitative, and short-term memory) was compared with previous findings of the same subjects at their initial test and 2-year follow up; the aim being to gain further insight into the clinical course of LNS over time. The results suggest that while the subjects generally continued to acquire new information and skills over time, their standardized scores declined, indicating that a plateau was reached in their skill levels relative to their peers, as also seen in other developmental disabilities. Deficits were noted in working memory, particularly on tasks that involve considering multiple features simultaneously.
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PMID:Cognitive functioning in Lesch-Nyhan syndrome: a 4-year follow-up study. 1035 10

Lesch-Nyhan syndrome is a genetic disorder resulting in hyperuricemia, choreoathetosis, mental retardation, and self-mutilation. The most salient feature of this disorder is the self-injurious behavior (SIB). Although the utility of behavioral interventions with SIB has been well documented, behavioral interventions with Lesch-Nyhan syndrome have been limited in number and long-term success. This article reviews the behavioral treatments that have been used in treating individuals with Lesch-Nyhan syndrome and discusses the strengths and weaknesses of these methods. Suggestions for future directions in the use of behavioral interventions for controlling SIB in Lesch-Nyhan syndrome are provided.
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PMID:A review of behavioral treatments used for Lesch-Nyhan syndrome. 1080 80

Lesch-Nyhan syndrome is an X-linked recessive disorder involving the purine metabolism, with resultant hyperuricemia, choreoathetosis, self-mutilation, and profound neurologic dysfunction. A deficiency of the enzyme hypoxanthine guanine phosphoribosyl-transferase is responsible for the disease. The human HPRT gene is located at Xq26-27 and consists of 57 base pairs. At least 2,000 mutations throughout the HPRT gene coding region from exon 1-9 have been reported. Four patients from three Chinese families were diagnosed with Lesch-Nyhan syndrome according to the clinical and laboratory findings. DNA studies revealed the first family (Patients 1 and 2) had a missense mutation in exon 3 of the HPRT encoding region. This novel mutation occurs in the hot spot of the HPRT gene. The second family (Patient 3) was found to have a missense mutation in exon 8 of the HPRT gene. The third family (Patient 4) carried a mutation in the splicing region of intron 4 of the HPRT gene. All three mutations were de novo.
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PMID:New mutations of the HPRT gene in Lesch-Nyhan syndrome. 1106 66

Lesch-Nyhan syndrome is a rare genetic disorder characterized by mental retardation, self-mutilation, choreoathetosis, and hyperuricemia. The disease is caused by a mutation in the hypoxanthine-guanine phosphoribosyltransferase gene and is transmitted as a sex-linked recessive disorder. Since hyperuricemia is the primary metabolic problem caused by a hypoxanthine-guanine phosphoribosyltransferase mutation, urologic evaluation and treatment is often necessary for children with this disease. We report a 3-year-old boy who presented with anuric renal failure secondary to bilateral obstructing uric acid calculi. The evaluation of T lymphocytes revealed a hypoxanthine-guanine phosphoribosyltransferase mutation consistent with Lesch-Nyhan syndrome. The diagnosis and urologic management of this disorder is discussed.
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PMID:Lesch-Nyhan syndrome presenting as acute renal failure secondary to obstructive uropathy. 1111 62

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) catalyzes the reutilization of hypoxanthine and guanine to the purine nucleotides IMP and GMP, respectively. HPRT deficiency is an X-linked disorder characterized by uric acid overproduction and variable neurologic impairment. The complete deficiency of HPRT is diagnostic of Lesch-Nyhan syndrome manifested by choreoathetosis, spasticity, mental retardation, and self-injurious behavior. In some HPRT-deficient patients the enzyme defect appeared to be "partial" and the neurologic symptoms mild to severe (Kelley-Seegmiller syndrome). This has prompted the classification of HPRT deficiency in 2 distinct groups: Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome, which has created much confusion. A spectrum of clinical consequences of HPRT deficiency has been recognized in small series of patients, but the complete spectrum of the neurologic disorder has not been described in a single series of patients examined by the same observers. We analyzed our experience with 22 patients belonging to 18 different families with HPRT deficiency diagnosed at "La Paz" University Hospital in Madrid over the past 16 years. The clinical spectrum of these HPRT-deficient Spanish patients was similar to the different phenotypes occasionally reported in the literature, in some cases diagnosed as Lesch-Nyhan "variants." The clinical, biochemical, enzymatic, and molecular genetic studies on these 22 patients allowed us to delineate a new classification of HPRT deficiency. Based on the neurologic symptoms, dependency for personal care, HPRT activity in hemolysate and in intact erythrocytes, and predicted protein size, patients were classified into 4 groups: Group 1 (2 patients), normal development with no neurologic symptoms, HPRT activity was detectable in hemolysates and in intact erythrocytes, and the mutation did not affect the predicted protein size. Group 2 (3 patients) mild neurologic symptoms that did not prevent independent lives, HPRT activity was detectable in intact erythrocytes, and the protein size was normal. Group 3 (2 patients), severe neurologic impairment that precluded an independent life, no residual HPRT activity, and normal protein size. Group 4 (15 patients), clinical characteristics of Lesch-Nyhan syndrome (some may not show self-injurious behavior), no residual HPRT activity, and in most (7 of 8 patients in whom the mutation could be detected) the mutation affected the predicted protein size. This classification of HPRT deficiency into 4 groups may be more useful in terms of accuracy, reproducibility, assessment for treatment trials and prognosis. The study of this Spanish series allows us to conclude that HPRT deficiency may be manifested by a wide spectrum of neurologic symptoms; the overall severity of the disease is associated with mutations permitting some degree of residual enzyme activity; and mutation analysis provides a valuable tool for prognosis, carrier identification, and prenatal diagnosis.
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PMID:The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Clinical experience based on 22 patients from 18 Spanish families. 1130 86

Different degrees of hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency are associated with hyperuricemia, uric acid nephrolithiasis and severe gout. Up to 25-30% of HPRT deficient patients, indicated as neurological variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may develop neurological manifestation, from mild to severe; the most serious ones manifesting in the devastating Lesch-Nyhan syndrome, characterized by choreoathetosis or self-mutilation. Here we present a 30 years old male patient suffering from gout and mild psycho-motor impairment without Lesch Nyhan disease despite severe HPRT deficiency residual activity 0.02% with hypoxanthine, no activity at all with guanine as a substrate. The Curto's theory that neurologic impairment is dependent on VGPRT/VHPRT ratio is not confirmed by our observations. The finding of such a severe HPRT deficiency in a non-Lesch-Nyhan patient needs further investigation. G6PD deficiency was also referred together with beta-thalassemic trait. We have studied purine and pyridine nucleotide metabolism in the erythrocytes and discussed the literature. The bone marrow sample shows a megaloblastyc aspect.
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PMID:Kelley-Seegmiller syndrome in a patient with complete hypoxanthine-guanine phosphoribosyltransferase deficiency. 1250 81

Lesch-Nyhan syndrome (LN) is a severe X-linked disorder of males characterized by hyperuricaemia, choreoathetosis, spasticity, mental retardation and self-mutilation. The disorder is caused by a wide spectrum of mutations distributed throughout the hypoxanthine phosphoribosyltransferase (HPRT) gene. Female carriers of LN display no clinical symptoms but are at 50% risk of passing on the affected gene to their male offspring. A couple who had a boy with LN were referred to Monash IVF for preimplantation genetic diagnosis (PGD) because the woman had undergone tubal ligation and the couple wanted to have another child. A test was developed for the causative mutation IVS8+6 T-->G mutation based on minisequencing primer extension that also incorporated the co-analysis of an informative tetranucleotide marker in intron 3 of the HPRT gene to identify allelic dropout. All four biopsied embryos from their first IVF cycle were diagnosed as unaffected, and transfer of two embryos in the cohort with the highest morphological quality resulted in a singleton pregnancy and the birth of a healthy girl. Direct mutation detection by mini-sequencing and parallel analysis of an informative linked marker provides an alternative strategy for molecular diagnosis of point mutations that will have useful application in PGD for other single gene disorders.
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PMID:Preimplantation diagnosis of Lesch-Nyhan using mini-sequencing primer extension. 1465 97


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