Lesch-Nyhan syndrome in an Arab family. Detection and biochemical manifestation of heterozygosity.
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.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity; D005260:Female; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood / Q000235:genetics*; D007557:Israel; D007926:Lesch-Nyhan Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011687:Purines / Q000096:biosynthesis; D012737:Sex Factors
D011687:Purines; D007041:Hypoxanthine Phosphoribosyltransferase