ASL variants cause argininosuccinate aciduria

Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the fourth reaction of the urea cycle, the cleavage of argininosuccinate to arginine and fumarate (Walker et al, 1990; Walker et al, 1997; Yu et al, 2001; reviewed in Nagmani et al, 2019). Mutations in ASL cause argininosuccinic aciduria (OMIM 207900), an autosomal recessive disorder that affects 1:70,000 to 1:218,000 live births (reviewed in Nagmani et al, 2019). Like other disorders of urea cycle enzymes, argininosuccinic aciduria is clinically diverse, with a severe neonatal form characterized by hyperammonemia, encephalopathy and respiratory alkalosis and a milder, late onset form that may be triggered by stress or infection (reviewed in Nagmani et al, 2019). Late onset alleles of ASL often retain residual activity, with heterozygous mutations interacting in vivo to restore a functional active site through intramolecular complementation (Yu et al, 2001; Trevisson et al, 2009; reviewed in Nagmani et al, 2019).

Summary from Reactome (R-HSA-9956529), read 2026-09-23.