Risk of serious illness in heterozygotes for ornithine transcarbamylase deficiency.
Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder associated with hyperammonemia. Heterozygous females have variable clinical expression, ranging from asymptomatic illness to recurrent episodes of hyperammonemic coma. We studied 17 OTC-deficient kindreds containing 114 women at risk for heterozygosity. Sixty-one of these women were designated heterozygotes by pedigree analysis, history of protein intolerance, protein tolerance tests, or DNA probe studies. Eleven (18%) of the 61 heterozygotes had experienced encephalopathic episodes; nine (82%) girls died during these episodes. Our findings indicate that there is a significant risk of symptomatic hyperammonemia in females heterozygous for OTC deficiency. We suggest that, within OTC-deficient kindreds, females at risk should be identified early, by means of protein tolerance tests and DNA probe studies. Those who develop significant hyperammonemia after a protein load should be considered for long-term alternate pathway therapy and should receive aggressive therapy during hyperammonemic episodes.
D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics*; D000641:Ammonia / Q000097:blood*; D002675:Child, Preschool; D003128:Coma / Q000209:etiology; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D012306:Risk; D014960:X Chromosome
D000641:Ammonia