Background Ornithine transcarbamylase (OTC) deficiency presents most commonly with neonatal hyperammonemic coma. The gene is on the X chromosome, but the disease may manifest as a dominant trait. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical disease occurs in adulthood.
Objective To document the clinical and metabolic consequences of a mutation in the OTC gene.
Design Case reports.
Setting A metabolic/biochemical genetic referral service.
Main Outcome Measures Clinical and biochemical observations in 3 generations of a family.
Results A mutation in codon 208 of exon 6 in the OTC gene was found in a family in which the proband died of hyperammonemia at 52 years of age.
Conclusions Diagnosis of late-onset presentations of urea cycle defect in adults may be delayed. Heightened awareness could lead to effective treatment.
Ornithine transcarbamylase (OTC) deficiency is the most common of the urea cycle disorders. Defects in enzymes of the urea cycle lead to hyperammonemia, encephalopathy, and coma. Patients typically present in the neonatal period with metabolic decompensation. Some individuals, however, do not become symptomatic until much later in life. The OTC deficiency is caused by mutations in the OTC gene and is expressed in an X-linked dominant manner.
This article describes a 52-year-old man who died of hyperammonemia and cerebral edema. The diagnosis in this family was made by determining the mutation in the OTC gene in his heterozygous daughter. Prenatal diagnosis of OTC deficiency in her twin sons led to prompt and effective management.
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