Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.

BACKGROUND: Argininosuccinate lyase deficiency (ASLD) is a rare autosomal recessive urea cycle disorder (UCD) resulting from mutations in the ASL gene. Previous studies of ASLD in patients from China have predominantly been limited to individual case reports, lacking comprehensive cohort study. This study aimed to systematically evaluate the clinical features, biochemical abnormalities, and genetic mutations of Chinese ASLD patients, thereby enhancing the understanding of the unique characteristics of this population. METHODS: We conducted a retrospective analysis of clinical and genetic data from patients diagnosed with ASLD at Shanghai Xinhua Hospital between January 2011 and May 2024. RESULTS: The cohort consisted of 28 Chinese ASLD patients from Xinhua Hospital. The median age of symptom onset was 18 days (range: 2 days to 6 years). Five patients (17.9%) died within the first year, and 87.0% (20/23) of survivors exhibited developmental delay. Citrulline levels were elevated in all patients. 14 out of 16 (87.5%) who underwent platelet testing demonstrated elevated platelet counts. The median blood ammonia level was 172 µmol/L (range: 9-1911 µmol/L). Early-onset cases had significantly higher ammonia levels than late-onset cases ( P < 0.0001). Eight patients underwent liver transplantation, which normalized ammonia levels and liver function but did not prevent developmental delay. Genetic analysis identified 14 novel ASL variants. CONCLUSIONS: Our study represents the largest cohort of ASLD patients from China reported to date. Despite active interventions, including liver transplantation, the prognosis remains poor, with a high prevalence of developmental delays. The identification of 14 novel pathogenic variants significantly expands the known mutation spectrum of the ASL gene in this population.