Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosin...

The relationship between a complete deficiency of the purine enzyme hypoxanthine-guanine phosphoribosyltransferase and the neurobehavioural abnormalities in Lesch-Nyhan disease remains an enigma. In vitro studies using lymphoblasts or fibroblasts have evaluated purine and pyrimidine metabolism with conflicting results. This study focused on pyridine nucleotide metabolism in control and Lesch-Ny...

substrates and products have no effect. Fractionation of normal erythrocytes by hypotonic lysis reveals a decline in the specific activity of A-PRT as the red cells age. In patients with the Lesch-Nyhan syndrome, the decline in A-PRT activity with ageing of cells is much less marked. Furthermore, the concentrations of free PRPP are as much as 10-fold elevated in the erythrocytes of these childr...

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency: complete HPRT deficiency (Lesch-Nyhan syndrome) presenting with severe neurologic or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. A 3-ge...

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is pr...

AIM There are substantial differences in the amount of research concerned with different disorders. This paper considers why. METHODS Bibliographic searches were conducted to identify publications (1985-2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairmen...

Hypoxanthine phosphoribosyltransferase (HPRT) is a purine metabolic enzymewhich converts hypoxanthineor guanine into IMP or GMP.One of the interesting viewpoints of HPRT deficiency is that there are two types of clinical features caused by the genetic enzyme deficiency ( 1 and 2 forreview). Thus, the severe type of the disease designated Lesch-Nyhan' s syndrome is associated with hyperuricemia ...