WHO-ICD-10 version:2010
Endocrine, nutritional and metabolic diseases
Metabolic disorders
Mode of Inheritance
Autosomal recessive
Citrullinemia is a urea cycle disorder and type I citrullinemia is the classic form of the disease. It is characterized by the accumulation of ammonia and other toxic nitrogenous substances in the body and defects in the ASS1 gene. The ASS1 gene encodes argininosuccinate synthetase 1 enzyme, one of the enzymes involved in the urea cycle. Defects in the enzyme disrupt the urea cycle, causing the accumulation of several nitrogenous toxic compounds, including ammonia, causing the characteristic signs and symptoms of type I citrullinemia.
Type I citrullinemia itself can be of a common severe form and a less common milder form. The former manifests itself in the very first days of an affected infant's life in the form of severe lethargy, poor feeding, seizures and loss of consciousness. The milder form has its onset in childhood or early adulthood and is characterized by intense headaches, lethargy, ataxia, and balance and vision problems. Classic citrullinemia is estimated to affect about 1 in every 57,000 live births worldwide.
A diagnosis of classical citrullinemia can be confirmed upon the following: hyperammonimia, reduced plasma argininosuccinic acid and increased plasma citrulline levels, and reduced tissue assay of arginiosuccinate synthetase enzyme activity. Mutation analysis of the ASS1 gene is also available for a one-step detection. Management strategies include going on a high calorie-low protein diet, supplementation of arginine, and administration of sodium phenylbutyrate and L-carnitine. Hemodialysis is frequently used in times of emergency. Liver transplantation may also be required. It is important to limit exposure to infectious diseases.