Longitudinal Study of Urea Cycle Disorders

What is the purpose of this trial?

Who can participate?

Ages Eligible: Any
Gender Eligible: Both

Inclusion Criteria:

- Diagnosis of NAGS deficiency, defined as the detection of a pathogenic mutation or
decreased (less than 20 % of control) NAGS enzyme activity in liver

- Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I
enzyme activity in liver or an identified pathogenic mutation

- Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation,
linkage analysis in an affected family, less than 20% of control of OTC activity in
the liver, or elevated urinary orotate (greater than 20 uM/mM) following allopurinol
loading with absence of argininosuccinic acid

- Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to
10-fold elevation of citrulline in plasma, decreased AS enzyme activity in cultured
skin fibroblasts or other appropriate tissue, or identification of a pathogenic
mutation in the AS gene

- Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence
of argininosuccinic acid in the blood or urine, decreased AL enzyme activity in
cultured skin fibroblasts or other appropriate tissue, or identification of a
pathogenic mutation in the AL gene

- Diagnosis of ARG deficiency (Hyperargininemia), defined as a greater than or equal to
5-fold elevated arginine levels in the blood, decreased arginase enzyme levels in red
blood cells or other appropriate tissue, or identification of a pathogenic mutation
in the ARG gene

- Diagnosis of HHH Syndrome or ORNT deficiency, defined as a greater than or equal to
5-fold elevated plasma ornithine and homocitrulline levels in the urine, or a
pathogenic mutation in the ORNT1gene (SLC25A15)

- Diagnosis of CITR deficiency (Citrullinemia Type II), defined as elevated citrulline
levels in the blood and a pathogenic mutation in the citrin gene

- Pending diagnosis of a UCD, defined as laboratory values highly suggestive of a UCD
with symptomatic hyperammonemic episodes but without a verifiable diagnosis

Exclusion Criteria:

- Hyperammonemia caused by an organic academia, lysinuric protein intolerance,
mitochondrial disorder, congenital lactic academia, fatty acid oxidation defects, or
primary liver disease

- Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage
in the newborn period, and extreme prematurity)

What is the purpose of this trial?

show additional information...

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Who can participate?

Ages Eligible: Any
Gender Eligible: Both

Inclusion Criteria:

- Diagnosis of NAGS deficiency, defined as the detection of a pathogenic mutation or
decreased (less than 20 % of control) NAGS enzyme activity in liver

- Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I
enzyme activity in liver or an identified pathogenic mutation

- Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation,
linkage analysis in an affected family, less than 20% of control of OTC activity in
the liver, or elevated urinary orotate (greater than 20 uM/mM) following allopurinol
loading with absence of argininosuccinic acid

- Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to
10-fold elevation of citrulline in plasma, decreased AS enzyme activity in cultured
skin fibroblasts or other appropriate tissue, or identification of a pathogenic
mutation in the AS gene

- Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence
of argininosuccinic acid in the blood or urine, decreased AL enzyme activity in
cultured skin fibroblasts or other appropriate tissue, or identification of a
pathogenic mutation in the AL gene

- Diagnosis of ARG deficiency (Hyperargininemia), defined as a greater than or equal to
5-fold elevated arginine levels in the blood, decreased arginase enzyme levels in red
blood cells or other appropriate tissue, or identification of a pathogenic mutation
in the ARG gene

- Diagnosis of HHH Syndrome or ORNT deficiency, defined as a greater than or equal to
5-fold elevated plasma ornithine and homocitrulline levels in the urine, or a
pathogenic mutation in the ORNT1gene (SLC25A15)

- Diagnosis of CITR deficiency (Citrullinemia Type II), defined as elevated citrulline
levels in the blood and a pathogenic mutation in the citrin gene

- Pending diagnosis of a UCD, defined as laboratory values highly suggestive of a UCD
with symptomatic hyperammonemic episodes but without a verifiable diagnosis

Exclusion Criteria:

- Hyperammonemia caused by an organic academia, lysinuric protein intolerance,
mitochondrial disorder, congenital lactic academia, fatty acid oxidation defects, or
primary liver disease

- Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage
in the newborn period, and extreme prematurity)

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