N-acetyl
glutamate synthase (
NAGS) deficiency (OMIM #: 237310) is a rare
urea cycle disorder that usually presents early in life with
hyperammonemia. NAGS catalyzes the synthesis of N-acetyl
glutamate (NAG) which functions as an activator of the
carbamoyl phosphate synthetase-1 mediated conversion of
ammonia to
carbamoyl phosphate. The absence of NAG results in a proximal
urea cycle disorder which can result in severe neurologic sequelae secondary to
hyperammonemia and even death. Unlike the other
urea cycle disorders, a specific pharmacological treatment for
NAGS deficiency exists in the form of
carglumic acid, an analog of NAG. Here we present a 29-year-old previously healthy female who presented with
hyperammonemia and obtundation just after the birth of her first child. Exome sequencing revealed two novel variants in the NAGS gene, and plasma metabolomics revealed extremely low levels of NAG.
Carglumic acid treatment led to prompt resolution of her biochemical abnormalities and symptoms. She tolerated two subsequent pregnancies, 2 years and 6 years after her initial presentation, while taking
carglumic acid, and breastfed her third child, all without complications in the mother or children. This case report emphasizes the importance of considering
urea cycle disorders in previously-healthy adults presenting with neurological symptoms during periods of metabolic stress, including the postpartum period. It also highlights the efficacious and safe use of
carglumic acid during pregnancy and while breastfeeding.