UCD.- Citrullinemia. Several clinical forms. Argininosuccinic acid synthetase deficiency.
Incidence
Common in Saudi Arabia and Middle East. Probable # 1 in Saudi Arabia.
Clinical Characteristics
The neonatal form is most common everyplace, with fulminant lethargy, coma,seizures & hypotonia. Infantil form is less severe with recurrent vomiting, ataxia and seizures. A third form has Mental retard. Can be asymptomatic. In Japan a late form is seen. Citrullinemia is an autosomal recessive inherited condition due to arginosuccinate synthetase deficiency, an enzyme involved in the urea cycle. The deficiency causes hyperammonemic coma, accumulation of citrulline and orotic acid, and arginine deficiency (Citrullinemia type I). Onset usually occurs soon after birth with severe hyperammonemic coma which may be associated with lactic acidosis, but a chronic juvenile form also exists with anorexia, vomiting, hypotonia, growth and psychomotor retardation, and convulsions. Diagnosis is based on the presence of hyperammonemia and on the chromatography of plasmatic and urinary aminoacids showing major elevation of citrulline, glutamine and alanine, and low levels of arginine. Another finding is orotic aciduria. Patients with citrullinemia type I are treated with a strict, lifelong diet of very limited protein intake, associated with arginine and both sodium benzoate and phenylbutyrate supplementation. Citrullinemia type II is a moderate form, linked to a specific mutation frequent in Japan. It is characterised by a slight intellectual impairment without acute episode. Some mutations lead to a mild increase of the citrulline level, the pathogen effect of which has not yet been clearly understood. Some very severe forms have been treated with liver transplantation, even though citrulline concentration remains higher than normal. Antenatal diagnosis is feasible.
Precipitants
High protein intake, intercurrent infections, vomiting episodes.
Provocation Tests
After protein loading the ammonia levels go markedly up. Also orotic acid goes up.
Diagnostic Procedures
EB- liver. Orotic acid in urine, GC/MS in urine