Looking beyond severe hypertriglyceridemia when diagnosing adult-onset citrullinemia type II

Background: Adult-onset citrullinemia type II (CTLN2) is a rare autosomal recessive urea cycle disorder caused by mutations in the solute carrier family 25 member 13 (SLC25A13) gene, which encodes citrin–a mitochondrial transporter involved in the malate–aspartate shuttle. In adults, CTLN2 may present atypically as isolated hypertriglyceridemia, often misattributed to secondary dyslipidaemia. Case description: A 30-year-old Vietnamese male with longstanding severe hypertriglyceridemia, first identified at age 13, was referred after an episode of acute pancreatitis at age 28. At presentation, plasma triglyceride levels reached 34.61 mmol/l. Secondary causes were excluded. Genetic testing via next-generation sequencing revealed compound heterozygous SLC25A13 mutations: c.2T>C and c.1638_1660dup, resulting in p.Met1Thr and p.Ala554GlyfsTer17, confirming the diagnosis of CTLN2. Initiation of a low-carbohydrate, high-protein, low-fat diet combined with fenofibrate (145 mg/day) led to a rapid reduction in triglyceride levels, normalizing within two weeks and remaining stable over three months. The treatment was well tolerated, with no reported adverse effects. Conclusion: CTLN2 should be considered in young adults with persistent, unexplained, and severe hypertriglyceridemia. Dietary modification constitutes the cornerstone of management, with fibrates playing a supportive role.