Hypoxanthine-guanine phosphoribosyl transferase deficiency.

摘要: In man congenital lack of an enzyme the purine salvage system, hypoxanthineguanine phosphoribosyl transferase (HG-PRT E.C. 2.4.2.8), is mostly accompanied by a picture known as Lesch-Nyhan syndrome. The degree deficiency may vary from zero to few percent normal activity but correlation between severity HG-PRT and clinical has not been observed, no more than neurological dysfunction. But individuals with undetectable without syndrome have described. Patients partial clinically distinctive findings. Sometimes mild abnormalities are observed. Because marked overproduction uric acid severe gouty arthritis renal dysfunction often encountered in both complete deficiency. There considerable molecular heterogeneity man. Mutant enzymes exhibit different kinetic electrophoretic properties, indicating that there might be mutation on structural gene coding for HG-PRT. Lack disturbs interconversions profoundly. addition important function uptake bases hypoxanthine guanine into cell, effective inosine, guanosine adenosine also seems dependent Uptake intact red blood cells occurs according two component mechanism, one probably involving system. inheritance X-linked recessive it transmitted asymptomatic carrier females. Several methods introduced detection. As consequence X chromosome inactivation, these females mosaicism positive negative fibroblasts can demonstrated after cloning or selection selective medium. A rapid method involves direct measurements activities single hair roots scalp. develop less clonally, heterozygote encountered. detected antenatally demonstrating presence absence ammiotic fluid derived qualitatively autoradiography quantitatively ultramicrochemical small numbers cells. studies isolated metabolic defect corrected several ways. Metabolic cooperation leads apparently phenotype all cells, provided cell contact. evidence missing product derivative transferred mutant Apparent correction observed when deficient lymphocytes stimulated phytohaemagglutinin. first data suggestive genetic complementation human strains which hybrid synthesize functionally active HG-PRT, consistent view due mutation. Recent results show other interesting findings come experiments treated exogenous material (isolated DNA metaphase chromosomes) reactivate induce activity.