NeurometPlus

Incidence

Citrullinemia type I is inherited in an autosomal recessive manner.

Clinical Characteristics

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). Milder, childhood to adult-onset citrullinemia type I is suspected in individuals with recurrent lethargy, somnolence, mental retardation, and chronic or recurrent hyperammonemia. The late-onset form may be milder than that seen in the acute neonatal form, for unknown reasons. The chronic juvenile form 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.The episodes of hyperammonemia are similar to those seen in the acute neonatal form, but the initial neurologic findings may be more subtle because of the older age of the affected individuals. When episodes of hyperammonemia occur, they are similar to those seen in the acute neonatal form, but the neurologic findings may be more subtle because of the older age of the affected individuals. These can include intense headache, scotomas, migraine-like episodes, ataxia, slurred speech, lethargy, and somnolence. Individuals with hyperammonemia also display respiratory alkalosis and tachypnea. Without prompt intervention, increased intracranial pressure occurs, with increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death.

Precipitants

Protein intake.

Provocation Tests

Protein intake will elevate ammonia levels rapidly.

Diagnostic Procedures

EB-F, EB-L. Argininosuccinate synthase enzyme activity, measured in fibroblasts, liver, and in all tissues and cells in which ASS is expressed, is decreased. ASS is the only gene known to be associated with citrullinemia type I. Sequence analysis and linkage analysis are clinically available. Aminoacids in plasma quantitative. Plasma ammonia concentration: In the severe form of the initial plasma ammonia concentration may be 1000-3000 µmol/L. In the milder neonatal and in the adult form, a lower plasma concentration may be seen. (Adult upper limit of normal is <35µmol/L). Plasma quantitative amino acid analysis: Citrulline: Usually >1000 µmol/L. Normal is <50 µmol/L. Argininosuccinic acid: Absent. Arginine and ornithine: Low to normal range. Lysine, glutamine, and alanine: Increased. Urinary organic acids: Normal, except orotic acid may be detected as part of urinary organic acid analysis by GC/MS; however, the sensitivity depends upon the extraction method.