CLINICAL AND BIOCHEMICAL HETEROGENEITY IN FEMALES OF A LARGE PEDIGREEWITH ORNITHINE TRANSCARBAMYLASE DEFICIENCY DUE TO THE R141Q MUTATION

A large family with ornithine transcarbamylase deficiency due to mutat ion R141Q was ascertained through a propositus who presented with acut e neonatal hyperammonemic coma, Of 13 females at risk, 11 were evaluat ed clinically and had laboratory studies performed, Seven were found t o be heterozygous for the mutation, Of these seven, five had chronic c linical symptoms and two were asymptomatic, None of the heterozygotes had elevated plasma ammonia on random testing. Of the five symptomatic females, three had markedly elevated plasma glutamine levels on rando m testing, while two had levels in the upper range of normal, Plasma c itrulline and arginine levels were somewhat lower in the symptomatic i ndividuals but still within the normal range. Five heterozygotes who w ere tested had either spontaneous erotic aciduria or elevated erotic a cid following ingestion of allopurinol, whereas one unaffected female and one unaffected male had normal allopurinol tests, A higher than ex pected proportion of female heterozygous for the R141Q mutation were c linically and biochemically symptomatic but remained undiagnosed for m ans years, Plasma glutamine determination and allopurinol testing shou ld be performed in females who present with a combination of relativel y non-specific symptoms detailed in this report. (C) 1996 Wiley-Liss, Inc.