Argininosuccinate lyase deficiency (ASL deficiency)
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A neonate presents within the first few days of life with poor feeding, lethargy, and hyperammonemia. Plasma citrulline is elevated and argininosuccinic acid is present in plasma and urine. Hair examination reveals trichorrhexis nodosa.
AR; ASL (argininosuccinate lyase)
- Hyperammonemia (neonatal or late-onset)
- Elevated plasma citrulline (moderate)
- Argininosuccinic acid in plasma and urine (pathognomonic)
- Trichorrhexis nodosa (brittle hair with nodular swelling)
- Hepatomegaly, liver dysfunction
- Intellectual disability
- Seizures
- Can present as severe neonatal form or milder late-onset form
- On RUSP
- Plasma amino acids: elevated citrulline, presence of argininosuccinic acid
- Urine organic acids: argininosuccinic acid
- Molecular testing: ASL gene
- Acute: hemodialysis, nitrogen scavengers (sodium benzoate, sodium phenylbutyrate)
- Chronic: protein restriction, arginine supplementation, nitrogen scavengers
- Liver transplant in severe cases
- Variable; severe neonatal form has higher mortality
- Intellectual disability common even with treatment
- Liver complications may develop over time
ASL = Another Strand Lost: ASL deficiency is the urea cycle disorder associated with trichorrhexis nodosa (brittle, broken hair shafts with nodular weak points). "Another Strand Lost" reminds you that ASL deficiency causes hair to break and fall apart.
ASL is the 5th enzyme of the urea cycle: the cytosolic enzyme that cleaves argininosuccinic acid into arginine + fumarate. Deficiency causes argininosuccinic acid to accumulate (the pathognomonic finding).
Citrulline + Aspartate --> Argininosuccinate --> Arginine: ASS1 catalyzes the first step (citrullinemia type I when deficient), ASL catalyzes the second step (ASL deficiency when deficient). Both cause elevated citrulline, but only ASL deficiency shows argininosuccinic acid.