[Methylmalonacidemia].

DNA analysis of a male propositus with ornithine transcarbamylase (OTC) deficiency documented an A-to-C substitution in position +4 of intron 1. No other abnormalities were observed in the OTC gene, or at 563 bp upstream of the 5' site, which included a promoter region, or at 383 bp downstream of the termination codon, which included a polyadenylation signal sequence. This mutation produces an RsaI site in the sequence, which was used for prenatal monitoring in the fourth and fifth pregnancies. DNA from amniotic cells in the former case were positive for RsaI digestion and the SRY gene (sex determinant region Y), indicating hemizygosity for the mutant allele. OTC activity was not measurable, and mRNA of the OTC gene was not detected by Northern blotting in the affected fetal liver. RT-PCR (reverse transcription-PCR) demonstrated only the wild-type allele. Thus, the mutation interferes with RNA processing, and an extremely low amount of normally spliced mRNA for the OTC gene seems to have caused the disease in our patient. The fetus of the fifth pregnancy was a normal male, as confirmed postnatally.

Amino Acid Metabolism, Inborn Errors↗