JIMD Reports, Volume 40

Rajabi, Farrah, Rodan, Lance H, Jonas, Maureen M, Soul, Janet S, Ullrich, Nicole J, Wessel, Ann, Waisbren, Susan E, Tan, Wen-Hann, Berry, Gerard T, Farrah Rajabi, Lance H. Rodan, Maureen M. Jonas, Janet S. Soul, Nicole J. Ullrich, Ann Wessel, Susan E. Waisbren, Wen-Hann Tan, Gerard T. Berry, Rodan, Lance H., Jonas, Maureen M., Soul, Janet S., Ullrich, Nicole J., Waisbren, Susan E., Berry, Gerard T.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing is often abnormal in patients with OTCD, liver failure is uncommon on presentation. A 13-month-old female with no significant past medical history presented with irritability, right arm weakness, and decreased appetite. Initial workup revealed hepatic dysfunction with an INR of 3.4, ammonia level of 75 μmol/L, and abnormal brain MRI with gyral edema with restricted diffusion, and patchy signal abnormality in basal ganglia. The MRI findings led to a putative diagnosis of acute disseminated encephalomyelitis prompting corticosteroid treatment. As steroid treatment was begun, she developed significant hepatocellular dysfunction with ALT 2,222 U/L, AST 630 U/L, prolonged INR, and elevated ammonia (213 μmol/L). Neurologic signs resolved and her ammonia level decreased (43 μmol/L) without further intervention; however, she had ongoing acute liver failure with coagulopathy and episodic irritability, managed as seronegative autoimmune hepatitis with partial response to corticosteroid therapy. At 18 months of age she presented with severe irritability with markedly increased ammonia (417 μmol/L). Plasma amino acids obtained several days prior to this acute episode demonstrated elevation in glutamine (2,725 μmol/L) and alanine (1,459 μmol/L). Biochemical testing demonstrated elevation of urine orotic acid (>240.6 mmol/mol creatinine). Genetic testing confirmed a heterozygous nonsense mutation in the OTC gene (c.958C>T, R320X). After treatment with ammonia scavengers and a protein-restricted diet, hepatic function normalized and irritability resolved. The diagnosis of a urea cycle disorder should be considered in patients with unexplained hepatic dysfunction.