title: Biochemical and molecular study of mentally retarded patient with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.
abstract: Nucleotide metabolism was studied in erythrocytes of a mentally retarded child and family members. Partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency was found in the propositus and an asymptomatic maternal uncle. Studies in crude lysates demonstrated decreased apparent V(max) and slightly decreased apparent K(m) for hypoxanthine in both HPRT-deficient subjects. Genomic DNA analysis revealed a single nucleotide change with leucine-147 to phenylalanine substitution in both subjects; mother and grandmother were heterozygous carriers of the same defect. This new variant has been termed HPRT(Potenza). Increased erythrocyte concentration of NAD and rate of synthesis by intact erythrocytes were found in the patient; increased activities of nicotinic acid phosphoribosyltransferase (NAPRT) and NAD synthetase (NADs) were demonstrated in erythrocyte lysates, with normal apparent K(m) for their substrates and increased V(max). These alterations were not found in any member of the family, including the HPRT-deficient uncle. These findings show multiple derangement of nucleotide metabolism associated with partial HPRT deficiency. The enzyme alteration was presumably not the cause of neurological impairment since no neurological symptoms were found in the HPRT-deficient uncle, whereas they were present in the propositus' elder brother who had normal HPRT activity.
authors: Dipartimento di Biologia Molecolare, Sez. Chimica Biologica, Università di Siena, Via Fiorentina 1, 53100, Italy. micheli@unisi.it
authors: Vanna
authors: V
authors: Micheli
authors: Birgit S
authors: BS
authors: Gathof
authors: Marina
authors: M
authors: Rocchigiani
authors: Gabriella
authors: G
authors: Jacomelli
authors: Silvia
authors: S
authors: Sestini
authors: Luana
authors: L
authors: Peruzzi
authors: Laura
authors: L
authors: Notarantonio
authors: Barbara
authors: B
authors: Cerboni
authors: Giuseppe
authors: G
authors: Hayek
authors: Giuseppe
authors: G
authors: Pompucci
mesh_terms: D002648:Child; D002675:Child, Preschool; D004795:Enzyme Stability; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D007223:Infant; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011687:Purines / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism
chemical_list: D011687:Purines; D011725:Pyridines; D007041:Hypoxanthine Phosphoribosyltransferase