Ornithine transcarbamylase (OTC) deficiency is an X-linked recessive disorder that usually presents in the neonatal period. Late-onset presentation of OTC can cause mild to severe symptoms. We describe laboratory and clinical findings of late-onset presentations of OTC deficiency. We conducted a literature search using search terms “ornithine transcarbamylase deficiency,” “late onset presentation,” and “hyperammonemia” from January 1, 1987, to December 31, 2016, was performed. Only papers published in English were included. We searched on PubMed, MEDLINE, and Google Scholar. We also present 2 OTC deficiency cases. A total of 30 adult cases had late-onset presentation of OTC deficiency reported. The majority were women (57%) with a median age of 37 years. The median level of ammonia was 308 mmol/L and the mortality rate was 30%. Our case 1 was a 40-year-old woman who succumbed to neurologic complications after a hyperammonemia crisis following an increased protein intake. Our case 2 was a 43-year-old woman with seizures associated with increased ammonia levels. Our 2 case reports show the wide phenotypic variability and severity in late-onset presentation of OTC ranging from seizures to cerebral herniation. Our literature review is the first to detail published laboratory and neurologic sequelae of late-onset OTC deficiency.
WalkerV. Ammonia toxicity and its prevention in inherited defects of the urea cycle. Diabetes Obes Metab. 2009;11(9):823–835.
2.
ApplegarthDATooneJRLowryRB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000;105(1):e10.
3.
AlameriMShakraMAlsaadiT. Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report. J Med Case Rep. 2015;9:267.
4.
BaillyPNouryJBTimsitSBen SalemD. Teaching neuroimages: ornithine transcarbamylase deficiency revealed by a coma in a pregnant woman. Neurology. 2015;85(20):e146–e147.
5.
Ben-AriZDalalAMorryA. Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins’ diet. J Hepatol. 2010;52(2):292–295.
6.
BezinoverDDouthittLMcQuillanPM. Fatal hyperammonemia after renal transplant due to late-onset urea cycle deficiency: a case report. Transplant Proc. 2010;42(5):1982–1985.
7.
BijvoetGPvan der Sijs-BosCJWieldersJPGrootOA. Fatal hyperammonaemia due to late-onset ornithine transcarbamylase deficiency. Neth J Med. 2016;74(1):36–39.
8.
BlairNFCremerPDTchanMC. Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults. Pract Neurol. 2015;15(1):45–48.
9.
BogdanovicMDKiddDBriddonADuncanJSLandJM. Late onset heterozygous ornithine transcarbamylase deficiency mimicking complex partial status epilepticus. J Neurol Neurosurg Psychiatry. 2000;69(6):813–815.
10.
ChiongMABennettsBHStrasserSIWilckenB. Fatal late-onset ornithine transcarbamylase deficiency after coronary artery bypass surgery. Med J Aust. 2007;186(8):418–419.
11.
ChoiDELeeKWShinYTNaKR. Hyperammonemia in a patient with late-onset ornithine carbamoyltransferase deficiency. J Korean Med Sci. 2012;27(5):556–559.
12.
Gascon-BayarriJCampdelacreuJEstelaJReñéR. Severe hyperammonemia in late-onset ornithine transcarbamylase deficiency triggered by steroid administration. Case Rep Neurol Med. 2015;2015:453752.
13.
GaspariRArcangeliAMensiS. Late-onset presentation of ornithine transcarbamylase deficiency in a young woman with hyperammonemic coma. Ann Emerg Med. 2003;41(1):104–109.
14.
GilchristJMColemanRA. Ornithine transcarbamylase deficiency: adult onset of severe symptoms. Ann Intern Med. 1987;106(4):556–558.
15.
HashashJGThudiKMalikSM. An 18-year-old woman with a 15-cm liver mass and an ammonia level of 342. Gastroenterology. 2012;143(5):1157, 1401–1402.
16.
KleinODKostinerDRWeisigerK. Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male. Hepatol Int. 2008;2(3):390–394.
17.
LegrasALabartheFMaillotFGarrigueMAKouatchetAOgier de BaulnyH. Late diagnosis of ornithine transcarbamylase defect in three related female patients: polymorphic presentations. Crit Care Med. 2002;30(1):241–244.
MachadoMCFonsecaGMJukemuraJ. Late-onset ornithine carbamoyltransferase deficiency accompanying acute pancreatitis and hyperammonemia. Case Rep Med. 2013;2013:903546.
20.
MantoADe GennaroASerinoACozzolinoAColasanteAGLa RoccaMR. MRI in a woman with late onset ornithine transcarbamylase deficiency. Neuroradiol J. 2010;23(4):398–401.
21.
MukhtarADabbousHEl SayedR. A novel mutation of the ornithine transcarbamylase gene leading to fatal hyperammonemia in a liver transplant recipient. Am J Transplant. 2013;13(4):1084–1087.
22.
NakajimaHSasakiYMaedaT. Antepartum ornithine transcarbamylase deficiency. Case Rep Gastroenterol. 2014;8(3):337–345.
23.
NedermeijerSCvan den HoutJGeleijnsCde KlerkHCatsman-BerrevoetsCE. Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency. Eur J Paediatr Neurol. 2015;19(3):364–366.
24.
RushETHartmannJESkrabalJC. Late-onset ornithine transcarbamylase deficiency: an under recognized cause of metabolic encephalopathy. SAGE Open Med Case Rep. 2014;2:2050313X14546348.
25.
SinghSPalSDubreySW. Unusual cause of general malaise: a young woman with ornithine transcarbamylase deficiency. BMJ Case Rep. 2016;2016:bcr2015213768.
26.
ThurlowVRAsafu-AdjayeMAgalouSRahmanY. Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency. Ann Clin Biochem. 2010;47(pt 3):279–281.
27.
UpadhyayRBleckTPBuslKM. Hyperammonemia: what urea-lly need to know: case report of severe noncirrhotic hyperammonemic encephalopathy and review of the literature. Case Rep Med. 2016;2016:8512721.
28.
WoodGEMcNicholasJ. Coma query cause. BMJ Case Rep. 2015;2015:bcr2014205592.
29.
CaldovicLAbdikarimINarainS. Genotype-phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. J Genet Genomics. 2015;42(5):181–194.
30.
YamaguchiSBraileyLLMorizonoH. Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene. Hum Mutat. 2006;27(7):626–632.
31.
GrunewaldSFairbanksLGenetS. How reliable is the allopurinol load in detecting carriers for ornithine transcarbamylase deficiency?J Inherit Metab Dis. 2004;27(2):179–186.
32.
ThomasGH. High male: female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders. Am J Hum Genet. 1996;58(6):1364–1368.
33.
McCulloughBAYudkoffMBatshawML. Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. Am J Med Genet. 2000;93(4):313–319.
BrassierAGobinSArnouxJB. Long-term outcomes in Ornithine Transcarbamylase deficiency: a series of 90 patients. Orphanet J Rare Dis. 2015;10:58.
36.
Lichter-KoneckiUCaldovicLMorizonoHOrnithine transcarbamylase deficiency. In: PagonRAAdamMPArdingerHH, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 2013.
37.
HaberleJBoddaertNBurlinaA. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32.
38.
BarshopBABreuerJHolmJLeslieJNyhanWL. Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia. J Inherit Metab Dis. 1989;12(1):72–79.
39.
EnnsGMBerrySABerryGTRheadWJBrusilowSWHamoshA. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med. 2007;356(22):2282–2292.
40.
LheureuxPEPenalozaAZahirSGrisM. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence?Crit Care. 2005;9(5):431–440.
