A study on Presymptomatic recognition and prevention of late-onset ornithine transcarbamylase deficiency in male

点击翻译按钮获取中文摘要

1)Mutational analysis of ornithine transcarbamylase(OTC)gene in 14 male patients with late-onset presentation from 10 discrete families revealed 10 patients from 7 families carried the R40H mutation, 2 patients from 2 families harbored the Y55D mutation and 2 patients from one family had the R277W mutation. These observations were unique in that these patients had the common mutations, in contrast to patients with neonatal onset, who invariably have private mutations.2)The Y55D and R277W mutations were transmitted exclusively from maternal side to their offspring. The incidence of the R40H mutation generated de novo was estimated to be not more than 12%. Mother-to-child transmission of the R40H gene was observed in 10 pairs, while father-to daughter transmission was found only in 3 pairs. A higher reproductive loss in hemizygous male patients than in heterozygous females may have contributed to this difference. Two heterozygous female developed symptomatic diseases, indicating that prognosis of heterozygous females carrying this mutation is not always fair.3)Development of simple method to detect the 3 mutations was studied. Detection of the mutation by means of difference in Tm values of PCR products was first tried but reproducibility was poor. In stead, a multiplex PCR method is now being developed.4)Mutational analysis in 3 male patients with neonatal onset revealed discrete, novel mutations in each family.5)Analysis of prognostic factor of life revealed that concentration of lysine and the other 8 amino acids in plasma were found to be significant determinants.6)It was proved that an early diagnosis and conventional, though appropriate, intervention could improve outcome of a hyperammonemic crisis in the late-onset male patients.