Chronic Liver Disease in Urea Cycle Disorders

Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism.With
early diagnosis and improved treatments, the survival of individuals with UCDs has improved,
and this improved survival has led to unmasking of some long-term complications such as
hepatic dysfunction and progressive fibrosis in a subset of patients. Hepatic complications
in UCDs are quite variable and dependent upon the specific metabolic defect. Currently, there
are no guidelines for monitoring hepatic complications or extent of liver disease in UCDs.

The purpose of this study is: 1) To determine whether liver stiffness is higher in
individuals with ASS1D, ASLD, and ARG1D as compared to females with OTCD, and to assess liver
stiffness in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD), 2) To test
whether markers of hepatocellular injury and function and novel serum biomarker panels for
hepatic fibrosis provide evidence of chronic liver disease in individuals with ASS1D, ASLD,
and ARG1D as compared to OTCD and to assess these sample markers of hepatocellular injury and
function and novel serum biomarker panels for hepatic fibrosis in other UCDs (citrin
deficiency, NAGSD, CPS1D, and males with OTCD).

Inclusion Criteria:

1. Age > 5 years and < 60 years

2. Weight ≥ 11 kg

3. Males or females with a diagnosis of OTCD based on molecular or enzymatic testing.
Males or females with a diagnosis of CPS1D, citrin deficiency, NAGSD, ASS1D, ASLD or
ARG1D based on biochemical OR molecular, OR enzymatic testing

Exclusion Criteria:

1. History of hyperammonemia (blood ammonia greater than 100 micromoles/L) documented in
the medical record or reported by the patient in the 30 days preceding enrollment
visit

2. History of Liver transplantation

3. Current pregnancy

4. Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol
liver disease