Significant hepatic involvement in patients with ornithine transcarbamylase deficiency.
OBJECTIVE
To determine the frequency of significant liver injury and acute liver failure (ALF) in patients with ornithine transcarbamylase deficiency (OTCD), the most common urea cycle defect.


METHODS
In this historical cohort study, charts of 71 patients with OTCD at 2 centers were reviewed to assess the prevalence of ALF (international normalized ratio [INR] ≥2.0), liver dysfunction (INR 1.5-1.99), and hepatocellular injury (aspartate aminotransferase/alanine aminotransferase ≥250 IU/L).


RESULTS
More than one-half (57%) of the 49 patients with symptomatic OTCD had liver involvement; 29% met the criteria for ALF, 20% had liver dysfunction, and 8% had isolated hepatocellular injury. The prevalence of ALF was highest in the patients with more severe OTCD, including those with markedly elevated ammonia levels (>1000 μmol/L). Some patients with severe liver involvement (INR ≥2.0 and aspartate aminotransferase/alanine aminotransferase >1000 IU/L) had only moderate hyperammonemia (ammonia 100-400 μmol/L). ALF was the initial presenting symptom of OTCD in at least 3 of 49 symptomatic patients with OTCD.


CONCLUSIONS
Episodes of hepatocellular injury, liver dysfunction, and ALF were identified in a high proportion of children with symptomatic OTCD. The more severely affected patients had a higher likelihood of ALF. The diagnosis of a urea cycle defect should be considered in patients with unexplained ALF, liver dysfunction, or hepatocellular injury.
University of Colorado School of Medicine, Department of Pediatrics, Section of Clinical Genetics and Metabolism and Children's Hospital Colorado, Aurora, CO.
Renata C
RC
Gallagher
University of California, Los Angeles, Department of Pediatrics, Division of Genetics, Los Angeles, CA.
Christina
C
Lam
University of California, Los Angeles, Department of Pediatrics, Division of Genetics, Los Angeles, CA.
Derek
D
Wong
University of California, Los Angeles, Department of Pediatrics, Division of Genetics, Los Angeles, CA.|University of California, Los Angeles, Departments of Psychiatry and of Human Genetics, Los Angeles, CA.
Stephen
S
Cederbaum
University of Colorado School of Medicine, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, The Digestive Health Institute and Children's Hospital Colorado, Aurora CO.
Ronald J
RJ
Sokol
D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology*; D017114:Liver Failure, Acute / Q000453:epidemiology / Q000209:etiology; D008297:Male; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000150:complications*; D015995:Prevalence