Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family is reported where four males have developed hyperuricemia, renal damage and, except for the youngest person affected, gout at an early age. The disease appears to be inherited as an X-linked recessive metabolic error. Clinically the patients have developed classical, tophaceous gout before the age of 25 and have suffered repeated attacks of renal colic. Renal tubular damage with decreased ability to concentrate and acidify urine was seen in a family member of only 16 years of age. Progressive renal failure seems to develop slowly. None in the family has shown neurologic symptoms, and two of the four affected men are apparently of at least average intelligence, two slightly below average. One female carrier has repeatedly passed uric acid stones. Studies of the red blood cell lysate have shown a normal activity of enzyme hypoxanthine phosphoribosyltransferase, and an increased level of adenine phosphoribosyltransferase. Skin fibroblasts from affected family members grew normally in the presence of 8-azaguanine. Administration of azathioprine to the patients did not decrease their serum uric acid levels. This is the first family described with this type of disorder of the purine metabolism.
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PMID:Recessive X-linked hyperuricemia with gout and renal damage, normal activity of hypoxanthine phosphoribosyltransferase and resistance to azaguanine. 42 44

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).
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PMID:Complete deficiency of adenine phosphoribosyltransferase. Report of a family. 86 83

A family is described in which four affected males, spanning two generations, have hyperuricemia and gout accompanied by hematuria but are without severe neurologic involvement. The affected males were found to have markedly reduced levels of erythrocytic hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity; these were 5-12% with hypoxanthine and 0.5-3% with guanine as compared to controls. Erythrocytic adenine phosphoribosyltransferase (APRT) was approximately three-fold elevated in the affected individuals. The residual HGPRT activity in affected males enabled characterization of some of the properties of this mutation. The apparent Michaelis constants (km) for both hypoxanthine and guanine were essentially unchanged, whereas the km for PP-ribose-P was approximately 10-20-fold elevated for all four affected males. The enzyme was more sensitive to product inhibition by IMP and GMP than controls, and exhibited greater thermal lability at 65 degrees C than found with control lysates.
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PMID:Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase with reduced affinity for PP-ribose-P in four related males with gout. 620 22

Authors present a 10 year old boy with Lesch-Nyhan syndrome with self-inflicted mutilations to the lips, tongue and interior cheek wall, partially avoided by tooth extraction. Hand lesions were prevented by arm restriction. Born with anoxia and in spite of seizures for several years and a marked muscle stiffness, he is relatively aware of his surroundings. HGPRT activity in blood and hair was nil, while the APRT activity was increased. The mother, a maternal aunt and grandmother are not carriers. Hyperuricemia measured several times and treated with allopurinol is kept between 3 and 4 mg/dl and lastly under 3 mg after increasing dosage. Some years ago, elimination of acid uric stones in urine was observed without hematuria. It seems that recently stone elimination produced pain difficult to evaluate in this patient.
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PMID:[Report of a patient with Lesch-Nyhan syndrome caused by total deficiency of HGPRT and with normal activity in female family members]. 713 25

Information on a familial syndrome of hyperuricemia and renal disease with or without gout was obtained on 33 of 41 blood relatives: Nine had renal disease; abnormalities of the urinary sediments were minimal; serum uric acid levels were elevated in seven and were not measured in two. Hyperuricemia was noted in three additional family members without evidence of renal disease. Goulty arthritis (three patients) did not precede renal disease. One individual had hyperuricosuria. The following erythrocyte purine enzyme levels were normal: adenine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate, synthetase, adenosine deaminiase, and purine nucleoside phosphorylase. Renal biopsy specimens showed focal global and segmental sclerosis of glomeruli, occasional hypercellularity, foci of atrophic tubules, chronic interstitial inflammation, and folding and wrinkling of glomerular basement membrane without electron-dense deposits. There were no immunofluorescent abnormalities.
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PMID:Familial hyperuricemia and renal disease. 739 93

Although gout and hyperuricaemia are usually thought of as conditions of indulgent male middle age, in addition to the well-known uricosuria of the newborn, there is much of importance for the paediatric nephrologist in this field. Children and infants may present chronically with stones or acutely with renal failure from crystal nephropathy, as a result of inherited deficiencies of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) or of the catabolic enzyme xanthine dehydrogenase (XDH). Genetic purine overproduction in phosphoribosylpyrophosphate synthetase superactivity, or secondary to glycogen storage disease, can also present in infancy with renal complications. Children with APRT deficiency may be difficult to distinguish from those with HPRT deficiency because the insoluble product excreted, 2,8-dihydroxyadenine (2,8-DHA), is chemically very similar to uric acid. Moreover, because of the high uric acid clearance prior to puberty, hyperuricosuria rather than hyperuricaemia may provide the only clue to purine overproduction in childhood. Hyperuricaemic renal failure may be seen also in treated childhood leukaemia and lymphoma, and iatrogenic xanthine nephropathy is a potential complication of allopurinol therapy in these conditions. The latter is also an under-recognised complication of treatment in the Lesch-Nyhan syndrome or partial HPRT deficiency. The possibility of renal complications in these three situations is enhanced by infection, the use of uricosuric antibiotics and dehydration consequent upon fever, vomiting or diarrhoea. Disorders of urate transport in the renal tubule may also present in childhood. A kindred with X-linked hereditary nephrolithiasis, renal urate wasting and renal failure has been identified, but in general, the various rare types of net tubular wasting of urate into the urine are recessive and relatively benign, being found incidentally or presenting as colic from crystalluria. However, the opposite condition of a dominantly inherited increase in net urate reabsorption is far from benign, presenting as familial renal failure, with hyperuricaemia either preceding renal dysfunction or disproportionate to it. Paediatricians need to be aware of the lower plasma urate concentrations in children compared with adults when assessing plasma urate concentrations in childhood and infancy, so that early hyperuricosuria is not missed. This is of importance because most of the conditions mentioned above can be treated successfully using carefully controlled doses of allopurinol or means to render urate more soluble in the urine. Xanthine and 2,8-DHA are extremely insoluble at any pH. Whilst 2,8-DHA formation can also be controlled by allopurinol, alkali is contraindicated. A high fluid, low purine intake is the only possible therapy for XDH deficiency.
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PMID:Gout, uric acid and purine metabolism in paediatric nephrology. 843 71

The molecular and biochemical aspects of purine nucleotide biosynthesis through de novo and salvage pathways, the production of uric acid, and their regulation mechanisms are reviewed for further understanding of hyperuricemia and gout. The metabolic rate of purine nucleotide biosynthesis is chiefly determined by the regulation of the de novo pathway, especially amidophosphoribosyltransferase and PRPP synthetase, and the accumulation of uric acid results from the acceleration of de novo biosynthesis and catabolism of purine nucleotide or the decrease in urinary excretion of uric acid. Moreover, several enzyme mutations of purine nucleotide metabolism are also clinically important including gout with hyperactive HPRT and the deficiency of HPRT (Lesch-Nyhan syndrome), adenylosuccinate lyase, xanthine oxidase, APRT, PNP, or ADA (SCID) with gene therapy.
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PMID:[Metabolism of purine nucleotides and the production of uric acid]. 897 90

Lesch-Nyhan syndrome is associated with complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), characterized by hyperuricemia and severe neurological signs. The HPRT gene has been mapped to the q26 region on the long arm of the X-chromosome. We are taking care of a family of Lesch-Nyhan syndrome. A 14-year-old male was noted the growth disturbance at the age of 7 months and self-mutilation behavior characterized by compulsive biting of his lip and fingers at the age of 18 months. In 1987, at the age of 4, he was diagnosed as Lesch-Nyhan syndrome from neurologic signs and hyperuricemia (9.8 mg/dl). Neurological examination revealed mild mental and growth retardation, spasticity and hyperreflexia of lower extremities, choreoathetoid movements of extremities, and compulsive self-mutilation. The HPRT activity in erythrocytes of this patient was 0.02 nmol/min/mg hemoglobin (control value 1.76 +/- 0.06), and adenine phosphoribosyltransferase (APRT) activity was 1.08 nmol/min/mg hemoglobin (control value 0.43 +/- 0.06). Using polymerase chain reaction (PCR) method coupled with direct sequencing, we analyzed the nucleotide sequences of each exon from the genomic DNA as well as the entire HPRT coding region of the cDNA by RT-PCR method. In the HPRT gene from the patient, a guanine to adenine substitution at base position 209 in exon 3 was identified, which resulted in a single amino acid substitution of glycine with glutamic acid at codon 70. The family studies indicated that his mother, sister and grandmother were heterozygotes. PCR-restriction fragment length polymorphism (RFLP) utilizing Mnl I site which created by the mutation, was useful for detection of the mutant gene. We have identified a new missense mutation of the HPRT gene in a Japanese patient. This mutation was reported at the same codon as foreign mutants and mighty be indicative of a location of mutation activity in the HPRT gene.
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PMID:[A Japanese family with Lesch-Nyhan syndrome resulting from a new point mutation in hypoxanthine-guanine phosphoribosyltransferase gene]. 939 32

An 18-year-old man was admitted to our hospital because of convulsive seizure. He had psychomotor retardation and intellectual disability from childhood, and had been diagnosed with attention deficit-hyperactivity disorder when he was 12 years old. He showed mental deficit (Wechsler Adult Intelligence Scale-Revised: IQ 52) and tendon hyperreflexia without pathological reflexes, but no involuntary movements or self-injurious behavior. As he had hyperuricemia, we measured the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) in erythrocytes. While HPRT activity had decreased to 57.4% of normal, APRT activity had increased to 140.5% of normal. Genetic analysis revealed a single-base substitution (c.179A>G) in the third exon of the HPRT gene, which resulted in a missense mutation (p.H60R) of the 60th amino acid. His mother was a heterozygous carrier of this mutation and presented partial deficiency (73.3%) of HPRT activity. Lesch-Nyhan disease is a neurogenetic disorder caused by complete deficiency of the enzyme HPRT. Variant forms of the disease caused by partial deficiency of HPRT do not show the typical clinical features, or show only mild neurological manifestations; these diseases are jointly referred to as HPRT-related neurological disease (HRND). The present case was unique in that the patient diagnosed as having HRND showed relatively higher HPRT residual activity in erythrocytes.
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PMID:[Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase presenting seizure and psychomotor retardation: a case report]. 2542 May 63

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data. Patients with HPRT deficiency present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. We present a 9-year-old boy who experienced an episode of macroscopic hematuria with dysuria and left flank pain. He presented hyperuricemia and hyperuricosuria. HPRT and APRT activities were both normal in hemolysate; however, HPRT activity assayed in intact erythrocytes was 50% of control levels. A new missense point mutation c.424 A>G (T142A) was found in the HPRT1 gene. The apparent Michaelis constant (Km) for 5-phosphoribosyl-pyrophosphate assayed in patient hemolysate was 20-fold of control levels. In conclusion, we report a patient with HPRT deficiency who presented with both normal HPRT and APRT activity in hemolysate, in which the enzyme activity determined in intact erythrocytes was of diagnostic utility.
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PMID:Unapparent hypoxanthine-guanine phosphoribosyltransferase deficiency. 2878


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