Adult Presentation of Ornithine Transcarbamylase Deficiency: 2 Illustrative Cases of Phenotypic Variability and Literature Review

Abstract

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.

Keywords: hyperammonemia; intracranial hypertension; late-onset disorders; ornithine transcarbamylase deficiency; seizure.

Figure 1.

Urea cycle. ADP indicates adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; CoA, coenzyme A.

Figure 2.

Radiographic and transcranial Doppler data from case 1. (A) Computed tomography of the head with obliteration of the basal cisterns, (B) effacement of bilateral hemispheric sulci, (C) computed tomography angiography of the head; coronal maximum intensity projection sequence demonstrated decreased visualization of right internal carotid artery, middle cerebral artery, and distal left middle cerebral artery, (D) transcranial Doppler revealed elevated resistivity index and reversal of blood flow during insonation of the proximal right middle cerebral artery.