Prenatal counseling in heterozygotes for ornithine transcarbamylase deficiency.

ABSTRACT

X-linked ornithine transcarbamylase deficiency (OTCD) often leads to fatal neonatal hyperammonemia in affected males (hemizygotes). In prenatal management of subsequent pregnancies, families carrying female fetuses are often reassured of the low risk of clinically overt disease. We suggest that such reassurance may be misleading. While OTCD heterozygotes may show no symptoms or only mild protein intolerance, the clinical course in a fraction of children can include manifestations similar to those in affected males. We present three cases of symptomatic and previously undiagnosed OTCD heterozygotes to illustrate the potential severity of this condition. Significant improvement in function and growth followed diagnosis and treatment; however, two of the three children remain significantly developmentally delayed. While a quantitative risk estimate cannot be derived from these data, the cases are indicative of an adverse outcome in manifesting heterozygotes. Accordingly, OTCD carrier families should be counseled regarding the possibility of significant hyperammonemia, neurologic deficit, and the need for pharmacologic and dietary intervention in their heterozygote daughters.