Family studies in ornithine transcarbamylase deficiency

Six families with at least one infant each with confirmed ornithine transcarbamylase deficiency were investigated by DNA analysis. All the affected sons had died, and no DNA had been stored. Using the restriction endonucleases MspI and Bam HI three restriction fragment length polymorphisms were detected which led to eight distinct haplotypes. Using these results and those of protein loading tests that diagnosed heterozygote (carrier) status in some family members, some carriers were detected, and prenatal diagnosis was offered to two families. In two further families no polymorphisms were found and no prenatal diagnosis was possible. In the remaining two families prenatal diagnosis was impossible because of the lack of DNA from an affected or unaffected son, or in one case from the father, of an obligate carrier. These studies emphasise the importance of preserving tissue for DNA extraction from infants dying of inborn errors of metabolism, and also show the way in which information from conventional biochemical studies can complement diagnostic tests using DNA.