Argininosuccinate Lyase (ASL) Deficiency; Outcome of Patients with an Early Presentation at Johns Hopkins Aramco Healthcare (JHAH)

Abstract

Abstract Argininosuccinic aciduria (ASA) is an autosomal recessive inborn error of the urea disorder (UCD) cycle caused by mutation in the gene encoding argininosuccinate lyase (ASL). Here, we describe long-term complications and outcome of twelve Saudi Arab patients originated from four unrelated families diagnosed with ASA from January 1st 1983 to December 31st 2022 within Johns Hopkins Aramco Healthcare (JHAH). The age distribution was from 1 to 29 years with an average of 11.9. All patients manifested the classic severe neonatal phenotype. Despite of an early diagnosis, immediate medical intervention and good metabolic control, all the patients displayed variable degrees of cognitive impairment and neurologic dysfunction. Developmental delay and seizures disorder were seen in all of the affected patients. Other observed neuropsychiatric disorders were attention deficit hyperactivity and sleeping disorders. The previously recognized c.1060C > Tp(Q354X) genotype in Saudi Arab population was found to be associated with intractable seizures and psychomotor regression. This cohort study supports the former reports of high rate of neurologic complication in Argininosuccinate lyase deficiency contrasting with a lower rate of hyperammonemia.