Maternal health outcomes in ornithine transcarbamylase deficiency: A comparative analysis of pregnancies in symptomatic and asymptomatic heterozygotes

Abstract

Introduction: Ornithine transcarbamylase deficiency (OTCD, MIM: 311250) is an X-linked disorder of ureagenesis caused by pathogenic variants in OTC (MIM: 300461). Due to varying X-inactivation patterns, female heterozygotes can range from asymptomatic to severe disease with recurrent hyperammonemia. There is a paucity of data regarding the safety of pregnancy in symptomatic versus asymptomatic OTC heterozygotes. Existing case reports suggest a high risk of morbidity and mortality associated with pregnancy.

Materials and methods: This study investigated the maternal health outcomes from a large cohort of OTC heterozygote participants who were enrolled in a multicenter, observational, natural history study conducted by the Urea Cycle Disorders Consortium.

Results: We evaluated maternal morbidity and mortality from 109 pregnancies in 49 OTC heterozygotes and found that pregnancy was well-tolerated without metabolic decompensations in individuals with asymptomatic OTCD. Thirty-one participants (63.3 %) had a second pregnancy. Among individuals with symptomatic disease, hyperammonemia was observed in 5 of the 21 pregnancies. Three of these episodes were in a single individual across three different pregnancies. One individual required ICU admission. There was no maternal mortality in either group.

Conclusions: Our results indicate that pregnancy is well-tolerated in asymptomatic OTC heterozygotes, with no metabolic decompensations observed. Close monitoring with a metabolic center is strongly recommended for OTC heterozygotes in pregnancy, in particular for symptomatic individuals to mitigate the risk of metabolic decompensation.

Keywords: Hyperammonemia; Ornithine transcarbamylase deficiency; Pregnancy; Urea cycle disorder.