UCD.- Argininosuccinic aciduria Childhood form. Argininosuccinase deficiency
Incidence
Inherited as an autosomal recessive trait, argininosuccinic aciduria affects both sexes equally.
Clinical Characteristics
Arginosuccinicaciduria is an autosomal recessive inherited deficiency of arginosuccinate lyase, an enzyme involved in the urea cycle. This leads to hyperammonemia and arginine deficiency. Onset occurs either soon after birth, with severe hyperammonemic coma that often proves to be fatal (see Neonatal form), or during childhood, with hypotonia, growth failure, anorexia and chronic vomiting or behavioral disorders. Onset can also occur later with hyperammonemic coma or behavioral disorders that simulate psychiatric disorders. Significant hepatomegaly and trichorrhexix nodosa are common observations. Diagnosis is made by the existence of hyperammonemia and by chromatography of plasmatic and urinary organic acids that shows accumulation of arginosuccinic acid (ASA) and orotic aciduria. Patients are treated with a strict lifelong diet with very low amounts of protein intake, arginine supplementation, and sometimes sodium benzoate or sodium phenylbutyrate. Antenatal diagnosis can be performed either by direct measure of citrulline and ASA in amniotic fluid or by enzymatic assay.
Precipitants
Protein intake. Also intercurrent infections may precipitate hyperammonemia.
Provocation Tests
Protein loading test: Give breakfast with 1 gr protein/kg and measure ammonia, aminoacids, urine orotic acid q 2 h x 6 h. Orotic acid will go up.
Diagnostic Procedures
Diagnosis is made by clinical suspicion. It is essential to obtaining a blood ammonia level, which is elevated significantly in the symptomatic patient. This finding should lead to an immediate blood and urine amino acid quantitation, which confirms presence of argininosuccinic acid in both fluids. In addition, increased blood citrulline, glutamine, alanine, and lysine may be observed. Argininosuccinic acid lyase may be assayed in cultured fibroblasts, providing the definitive biochemical diagnosis. Urine orotic acid is elevated.