Peripartum Considerations in Ornithine Transcarbamylase Deficiency
Abstract Number: T1D-9
Abstract Type: Case Report/Case Series
Background: Ornithine transcarbamylase (OTC) deficiency is the most common enzymatic deficiency in the urea cycle, occurring in 1:14,000 births. (1) The urea cycle is a series of enzymatic reactions by the body that converts ammonia to urea so that it can be safely eliminated. As a result of this deficiency, toxic levels of ammonia can result during catabolic states when ammonia is produced from the breakdown of proteins. Symptoms can include lethargy, vomiting, coma, cerebral edema, and even death from hyperammonemia and hyperglutaminemia. OTC deficiency is inherited in an X-linked dominant pattern. However, female carriers can experience mosaicism and experience similar symptoms to affected men. The peripartum period is considered to be a particularly vulnerable time for hyperammonemic episodes, and there have been case reports of coma and brain death in carriers during this period. (2)
Case report: Two sisters with known OTC deficiency carrier status delivered at our institution in 2017, one via vaginal delivery and the other via cesarean delivery. A multidisciplinary plan of care was arranged ahead of their deliveries in conjunction with OBGYN, Pharmacy, and OB Anesthesiology guided by peripartum instructions given to the patients by their Metabolism specialist. These instructions included avoidance of a catabolic state with dextrose-containing maintenance fluids, ammonia levels drawn every 6 hours, and glucose drawn hourly. (3) Ammonul (sodium phenylacetate and sodium benzoate), the treatment of choice for hyperammonemia, was stocked ahead of time by pharmacy. Patient A was kept on D10 1/2NS at 125 ml/hr while in labor. Patient B was maintained on clear fluids with sugar up until 2 hours prior to her 8am scheduled cesarean delivery. Patient A had a peak ammonia level of 43 umol/L (ref: 0-53 umol/L). Patient B had a peak ammonia level of 41 umol/L. There were no complications.
Discussion: OTC deficiency is a potentially lethal disease during the peripartum period even in asymptomatic carriers though it is not well-known to anesthesia providers. Though our 2 cases were uneventful, coordination ahead of time was important to ensure the appropriate pharmacologic treatment was available. In a true hyperammonemic emergency (3x the reference ammonia level of 0-53 umol/L), it is reassuring to know that ammonia can also be removed by emergent hemodialysis.
1.Brusilow S et al. Urea cycle enzymes. In: Scriver C, et al. The Metabolic and Molecular Basis of Inherited Disease. 8th ed. New York: McGraw-Hill; 2000:1909–1963
2.Arn PH, et al. Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus. A cause of postpartum coma. N Engl J Med 1990;322:1652–1655
3.Mendez-Figueroa H, et al. Management of Ornithine Transcarbamylase Deficiency in Pregnancy. Am J Perinatol 2010 Nov;27(10):775-84