Biochemical Profile of Argininosuccinate Synthase 1 Deficiency Patients from a Referral Hospital in Brazil

Argininosuccinate synthase 1 deficiency (ASS1D) is an autosomal recessive disease that occurs due to a defect in the enzyme that catalyses the condensation of citrulline and aspartate into argininosuccinate in the urea cycle. Outcomes are highly variable as the disease can present as neonatal, late-onset, asymptomatic, non-hyperammonemic or postpartum. However, most neonatal ASS1D hyperammonemic crises can be extremely severe and often lead to death. In this study, we describe and analyse the biochemical profile of ten ASS1D patients from Hospital de Clínicas de Porto Alegre (HCPA), a referral hospital in Brazil. All the data were collected from their medical records under approved project number 2020–0562. The ten individuals who had a mean age of 2.11 years (SD±4.85) were diagnosed with ASS1D. The amino acid profile showed increased citrulline blood levels [562.95 μM/L (SD±554; n=10); reference values: 5.60–16.26 μM/L to individuals 30 days and 8.19–20.11 μM/L to 30 days] as well as increased glutamine [3541 μM/L (SD± 4929; n = 3); reference values: 376–709 μM/L to 30 days and 246–823 μM/L 30 days] and alanine (1468 μM/L (SD± 1758; n = 5); reference values: 131–710 μM/L to 30 days and 143–547 μM/L to 30 days]. Along with the amino acid profile, hyperammonemia (ammonia levels: 1464 μM/L, reference values: ≤80) and high excretion of urinary orotic acid [206 μg/mg of creatinine (SD±12.2; n=3) reference values: ≤14] were the principal laboratory findings. Hypotony, hypoactivity, metabolic acidosis, convulsive seizures, vomiting, and coma were the most common clinical symptoms observed. Three patients (30%) died due to severe ASS1D outcomes. With this analysis, we want to highlight the main clinical and laboratory findings observed in ASS1D to help the clinical staff rapidly recognise the signs and symptoms to provide urgent treatment to patients.