Severe Familial Hypertriglyceridemia in a Child with Compound Heterozygous Pathogenic APOA5 Variants: A Case Report...

Familial hypertriglyceridemia (FHTG) is a rare inherited lipid disorder that may present with severe phenotypes when caused by compound heterozygous or biallelic APOA5 variants. We report a male child diagnosed at 2.5 years of age with severe hypertriglyceridemia, who exhibited serum triglyceride levels persistently above 10 mmol/L (≈ 885 mg/dl) despite adherence to a low-fat diet and pharmacotherapy including fibrates, omega-3 fatty acids, and statins. Representative triglycerides at presentation were 11.6 mmol/L (≈ 1029 mg/dl). During follow up, the patient experienced an acute abdominal pain episode with triglycerides nearing 20 mmol/L (≈ 1770 mg/dL), managed conservatively under suspicion of pancreatitisOral glucose tolerance testing showed a high-normal insulin response (peak 84.5 mIU/L, below the insulin-resistance threshold of 100-150 mIU/L), which prompted addition of metformin. Over a decade, despite normal growth and clinical well-being, biochemical control remained suboptimal. This case illustrates the clinical utility of early genetic testing in pediatric dyslipidemias and highlights limitations of traditional treatments in monogenic severe FHTG. Emerging therapies, including antisense oligonucleotides and ANGPTL3 inhibitors, may hold future promise.