Management of Ornithine Transcarbamylase Deficiency in Pregnancy

ABSTRACT

Ornithine transcarbamylase (OTC) deficiency is the most common enzymatic deficiency in the urea cycle. In catabolic states, such as the intrapartum and immediate postpartum periods, hyperammonemic comas with permanent neurological damage and death can develop. We report six cases of OTC deficiency during pregnancy managed at our institution and review the literature on OTC deficiency during pregnancy. Using the patient database from our Metabolic Clinic, pregnant OTC deficiency carriers were identified. The antenatal, intrapartum, and postpartum periods were analyzed. Corresponding literature was reviewed and an extensive multidisciplinary management plan developed. All six pregnant women had favorable outcomes. No hyperammonemic episodes occurred, and intensive care unit admissions and hemodialysis were not required. Although risk to women with OTC deficiency during the intra- and postpartum period exists, multidisciplinary management and a coherent plan usually result in successful labor, delivery, and postpartum. A comprehensive plan for patients who develop hyperammonemia is recommended.

KEYWORDS

Pregnancy - OTC deficiency - urea cycle disorder

REFERENCES

• 1 Brusilow S, Horwich A. Urea cycle enzymes. In: Scriver C, Sly W, Valle D, Childs B, Kinzler K, Vogelstein B The Metabolic and Molecular Basis of Inherited Disease. 8th ed. New York; McGraw-Hill 2000: 1909-1963
• 2 Rowe P C, Newman S L, Brusilow S W. Natural history of symptomatic partial ornithine transcarbamylase deficiency.  N Engl J Med. 1986;  314 541-547
• 3 Arn P H, Hauser E R, Thomas G H, Herman G, Hess D, Brusilow S W. Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus. A cause of postpartum coma.  N Engl J Med. 1990;  322 1652-1655
• 4 Legras A, Labarthe F, Maillot F, Garrigue M-A, Kouatchet A, Ogier de Baulny H. Late diagnosis of ornithine transcarbamylase defect in three related female patients: polymorphic presentations.  Crit Care Med. 2002;  30 241-244
• 5 Batshaw M L, Roan Y, Jung A L, Rosenberg L A, Brusilow S W. Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency.  N Engl J Med. 1980;  302 482-485
• 6 Peterson D E. Acute postpartum mental status change and coma caused by previously undiagnosed ornithine transcarbamylase deficiency.  Obstet Gynecol. 2003;  102(5 Pt 2) 1212-1215
• 7 Schimanski U, Krieger D, Horn M, Stremmel W, Wermuth B, Theilmann L. A novel two-nucleotide deletion in the ornithine transcarbamylase gene causing fatal hyperammonia in early pregnancy.  Hepatology. 1996;  24 1413-1415
• 8 Redonnet-Vernhet I, Rouanet F, Pedespan J M, Hocke C, Parrot F. A successful pregnancy in a heterozygote for OTC deficiency treated with sodium phenylbutyrate.  Neurology. 2000;  54 1008
• 9 Cordero D R, Baker J, Dorinzi D, Toffle R. Ornithine transcarbamylase deficiency in pregnancy.  J Inherit Metab Dis. 2005;  28 237-240
• 10 Verlinsky Y, Rechitsky S, Verlinsky O, Strom C, Kuliev A. Preimplantation diagnosis for ornithine transcarbamylase deficiency.  Reprod Biomed Online. 2000;  1 45-47
• 11 Enns G M, Berry S A, Berry G T, Rhead W J, Brusilow S W, Hamosh A. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.  N Engl J Med. 2007;  356 2282-2292
• 12 Lee B, Goss J. Long-term correction of urea cycle disorders.  J Pediatr. 2001;  138(1 Suppl) S62-S71
• 13 Berry G T, Steiner R D. Long-term management of patients with urea cycle disorders.  J Pediatr. 2001;  138(1 Suppl) S56-S60 discussion S60-S61
• 14 Wilcken B. Problems in the management of urea cycle disorders.  Mol Genet Metab. 2004;  81(Suppl 1) S86-S91