Paediatrics: Urea cycle disorders

Urea cycle disorders

The urea cycle disorders are a group of conditions in which enzyme defects result in the accumulation of nitrogen in the form of ammonia, which is a highly toxic substance causing irreversible brain damage. Clinical presentation may be in the first few days of life. Hyperammonaemia (usu-ally severe) results in:

•   coma;

•   convulsions and vomiting.

Clinical confusion with septicaemia is common. In the older child, patients may present with:

•   psychomotor retardation;

•   growth failure;

•   vomiting;

•   behavioural abnormalities;

•   recurrent cerebellar ataxia and headache.

It is essential to monitor the blood ammonia in any patient with unex-plained neurological symptoms.

The urea cycle disorders

•   N-acetylglutamate synthetase deficiency (NAGS)

•   Carbamyl phosphate synthetase deficiency (CPS)

•   Ornithine transcarbamylase deficiency (OTC)

•   Argininosuccinic acid synthetase deficiency (citrullinaemia; AS)

•   Argininosuccinase acid lyase deficiency (argininosuccinic aciduria; AL/ ASA)

•   Arginase deficiency (arginaemia; AL/ASA)

All are autosomal recessive except for ornithine transcarbamylase defi-ciency (X-linked). Individuals with childhood or adult onset disease may have a partial enzyme deficiency

Diagnosis

Plasma concentrations of ammonia are elevated, glutamine and alanine (the major nitrogen-carrying amino acids) are usually high, and arginine is low. Specific urea cycle defects can be diagnosed by their characteristic plasma and urine amino acid profiles.

Treatment 

Management of dietary protein intake with essential amino acids and restriction of protein intake to suppress ammonia formation.