Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1.

Carbamoyl phosphate synthetase I (CPS1) deficiency is an autosomal recessive metabolic disorder affecting the first enzymatic step of urea cycle. We report a consanguineous family in which the index patient died at 11 days of age from a severe form of CPS1 deficiency. Initial diagnosis was based on clinical histopathological, and enzymatic investigations. Direct sequencing of the complete CPS1 coding region revealed a disease-associated homozygous Thr544Met mutation in CPS1. On the basis of the molecular data, prenatal diagnosis was established for genomic DNA and performed at gestational week 12, after chorionic villus sampling. The fetus was homozygous for the Thr544Met mutation, and termination of pregnancy was elected. Histopathological signs of the hepatocellular metabolic disorder similar to that of the index patient were found in fetal liver thus giving morphological evidence for this hereditary error of urea cycle function as early as gestational week 12.