Arginine:glycine Amidinotransferase Deficiency: the Third Inborn Error of Creatine Metabolism in Humans

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2001 Sep 14

PMID 11555793

Citations 63

Authors

C B Item

S Stockler-Ipsiroglu

C Stromberger

A Muhl

M G Alessandri

M C Bianchi

M Tosetti

F Fornai

G Cioni

Affiliations

Soon will be listed here.

Abstract

Arginine:glycine amidinotransferase (AGAT) catalyzes the first step of creatine synthesis, resulting in the formation of guanidinoacetate, which is a substrate for creatine formation. In two female siblings with mental retardation who had brain creatine deficiency that was reversible by means of oral creatine supplementation and had low urinary guanidinoacetate concentrations, AGAT deficiency was identified as a new genetic defect in creatine metabolism. A homozygous G-A transition at nucleotide position 9297, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (T149X), resulted in undetectable cDNA, as investigated by reverse-transcription PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. Recognition and treatment with oral creatine supplements may prevent neurological sequelae in affected patients.

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