Significant hepatic involvement in patients with ornithine transcarbamylase deficiency

Abstract

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.

Study design: 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.

Conclusion: 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.

Copyright © 2014 Mosby, Inc. All rights reserved.

Figures

Figure 1

Time course of plasma ammonia, ALT, and INR in a severe OTCD female during her initial hospitalization at 19 months of life. Dietary treatment was instituted on day 7, and full medical therapy on day 10. The vertical black arrow indicates the time point collected for the chart review in this hyperammonemic episode (part 2, case 8; Table III).

Figure 2

Summary of types of liver injury present in cases of OTCD followed at the two metabolic disease centers.