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 deficiency of adenine phosphoribosyltransferase (APRT) enzyme activity to approximately 40% of normal has been found in erythrocytes from a young woman aged 24 years, who had suffered from recurrent gouty arthritis since 11 years of age. She also demonstrated considerable, although asymptomatic, renal impairment with a creatinine clearance of one-third normal. Her father had suffered from gouty arthritis but had a normal APRT activity; he was obese, had a high purine intake and was a regular beer drinker. The patient's mother was asymptomatic with a normal serum urate concentration, but demonstrated a similar reduction in APRT activity to that of her daughter. Eleven other asymptomatic members of the family also demonstrated a similar reduction in APRT activity in erythrocyte lysates. The pattern of inheritance was consistent with autosomal transmission. Concentrations of phosphoribosylpyrophospate (PRPP) in erythrocytes were within normal limits both in the subjects with deficient, and in those with normal, APRT activity. Partial purification of APRT enzyme from erythrocytes of the index case did not reveal any difference from the normal enzyme as far as Michaelis constants, heat stability, or mobility in polyacrylamide gel was concerned. No primary abnormality of lipoprotein metabolism was demonstrated either in the propositus or in other members of her family. Study of urate metabolism in the propositus indicated that, although urate production was within the normal range in absolute terms, there was increased incorporation of glycine into produced urate, usually taken as one index of de novo urate production. Impaired renal excretion of urate was also shown. Although detailed study of urate metabolism has not been undertaken in other family members with APRT deficiency, no conclusive relationship has yet been demonstrated between APRT deficiency and disordered urate metabolism.
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PMID:Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease. 106 47

Acute renal failure (ARF) is not listed as a usual form of presentation in hypoxanthine-guanine phosphoribosyltransferase deficiency, despite the gross uric acid overproduction in the defect. We found that a third of such patients may present in ARF when the urinary uric acid/creatinine ratio may be normal, not raised, and the defect may be suspected from the disproportionate increase in plasma uric acid. This is important in view of the potential confusion of uric acid with 2,8-dihydroxyadenine, the even more insoluble purine excreted in the other salvage enzyme disorder, adenine phosphoribosyltransferase deficiency. In that disorder, presentation in ARF is well recognized, the uric acid/creatinine ratio is also normal, but plasma urate is not raised. Our combined experience in these two disorders underlines the importance of early recognition and treatment with carefully adjusted doses of allopurinol, which may reverse or postpone renal failure.
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PMID:Purine enzyme defects as a cause of acute renal failure in childhood. 264 13

A large Arab family affected with the rare X-linked Lesch-Nyhan syndrome is reported on. Two hemizygous boys, two and nine years of age, had the classical biochemical and clinical-neurological syndrome. The activity of erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was below the detectable limit (greater than 0.1% of normal). They were mentally and physically retarded and exhibited spasticity and choreoathetosis; the older of the two also exhibited self-mutilation. The mother and three of her seven daughters, all clinically asymptomatic, were proven to be heterozygous for HGPRT deficiency, by demonstration of an increased rate of de novo purine synthesis in cultured skin fibroblasts. Erythrocyte HGPRT activity was normal in the three heterozygous daughters, but was significantly reduced in the mother. However, in all four heterozygotes, erythrocyte HGPRT/adenine phosphoribosyltransferase ratio was lower than in all other family members. All heterozygotes had blood uric acid levels within the normal range, although higher than in the normal women in the family. The ratio uric acid/creatinine concentration in the urine was significantly elevated in one of the heterozygotes, and in the upper normal limit in two others, indicating excessive purine production.
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PMID:Lesch-Nyhan syndrome in an Arab family. Detection and biochemical manifestation of heterozygosity. 732 17

In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. Treatment with allopurinol controls formation of DHA stones by inhibiting XDH activity. Kidney disease in APRT-deficient mice resembles that seen in humans. By age 12 wk, APRT-deficient male mice are, on average, mildly anemic and smaller than normal males. They have extensive renal interstitial damage (assessed by image analysis) and elevated blood urea nitrogen (BUN), and their creatinine clearance rates, which measure excretion of infused creatinine as an estimate of glomerular filtration rate (GFR), are about half that of wild-type males. APRT-deficient males treated with allopurinol in the drinking water had normal BUN and less extensive visible renal damage, but creatinine clearance remained low. Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.
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PMID:Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency. 968 17