Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 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.
 ...
PMID:Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease. 106 47

Three brothers who developed acute gouty arthritis at ages 16, 20 and 26 years were found to have increased plasma urate. Erythrocyte hypoxanthine phosphoribosyltransferase (HPRT) activity was less than 1% of normal and adenine phosphoribosyltransferase (APRT) activity was increased 2-3-fold. This variant, HPRTEdinburgh, was further studied using lymphoblast lines established from these patients and the following observations are consistent with a mutation involving a single amino acid substitution. Lymphoblasts from these patients had 0.9-1.6% of control HPRT activity which was 8-fold more labile than control activity at 75 degrees C. Isoelectric focusing of the variant protein in polyacrylamide gels indicated a pI of 6.5-6.7 which is more basic than normal HPRT, pI 6.0-6.3. The Michaelis constants were increased: 10-fold for hypoxanthine from 1.3 to 13 mumol/L, and 5-fold for PP-ribose-P from 6 to 30 mumol/L, for control and variant respectively. The Ki for product inhibition by GMP was marginally increased in the variant. Northern blot analysis of variant lymphoblast RNA indicated normal amounts of the expected 1.6 kilobase messenger RNA.
 ...
PMID:Hypoxanthine-guanine phosphoribosyltransferase deficiency in three brothers with gout: characterization of a variant, HPRTEdinburgh, having altered isoelectric point, increased thermal lability and normal levels of messenger RNA. 251 72

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.
 ...
PMID:Familial hyperuricemia and renal disease. 739 93