Maternal gonadal mosaicism causing ornithine transcarbamylase deficiency

Ornithine transcarbamylase (OTC) deficiency (McKusick 311250), an X-linked inherited disorder, often presents in males with severe neonatal onset of h yperammonemia, Maternal gonadal mosaicism in OTC deficiency was postulated previously, but no cases have been reported, We report on a family in which two consecutive males were affected with OTC deficiency, which was proven biochemically with characteristic metabolites and absent enzyme activity in liver. OTC genotyping in both brothers showed a new mutation in exon 6 (Me t206Arg: ATG-->AGG), which encodes part of the equatorial H6 alpha-helix. B iochemical investigations confirmed normal results in the mother and grandm other and the absence of OTC activity in the affected males. Grenotyping of the mother and grandmother was performed on peripheral blood leukocytes an d shin fibroblasts and showed no mutation in the somatic cells. The recurre nce of OTC deficiency in offsprings of a woman with normal genotype strongl y suggests gonadal mosaicism, Gonadal mosaicism needs to be considered when counseling couples in which the mother has had a previously affected child with OTC deficiency but apparently is not a carrier. Genet. (C) 1999 Wiley -Liss, Inc.