Endocrine Abstracts

JOINT1695

Background: Severe hypertriglyceridemia and dyslipidemia in infancy are rare, often presenting with nonspecific signs that complicate early diagnosis and management. Genetic causes, such as mutations in key triglyceride metabolism proteins, are frequently implicated. GP1HBP1 (Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) is critical for the interaction between lipoprotein lipase (LPL) and triglyceride-rich lipoproteins. Mutations in GP1HBP1 impair triglyceride clearance, leading to extreme hyperchylomicronemia, characterized by markedly elevated triglycerides, lipemia retinalis, and risk of acute pancreatitis¹. Early recognition of genetic hyperlipidemias is crucial for prompt intervention and prevention of complications².

Case Presentation: We report a 20-day-old neonate presenting with fever and incidentally noted cloudy blood samples. Lipid profile showed extreme hyperlipidemia: total cholesterol 702 mg/dL, triglycerides 12,583 mg/dL, HDL 51 mg/dL, and VLDL 2,517 mg/dL. The infant, born full-term with no neonatal complications, had no xanthomas, xanthelasmas, or family history of dyslipidemia. Fundoscopy revealed lipemia retinalis; abdominal ultrasound was normal. Genetic testing identified a homozygous pathogenic GP1HBP1 variant, confirming autosomal recessive chylomicronemia syndrome¹. Management included a low-fat maternal diet (as the infant was exclusively breastfed) and omega-3 fatty acid supplementation (2 g/day)³.

Discussion: This case highlights the need to consider genetic dyslipidemias in neonates with severe hypertriglyceridemia. GP1HBP1 mutations disrupt LPL activity, causing impaired triglyceride metabolism¹. Management focuses on dietary fat restriction, omega-3 supplementation, and close monitoring to prevent complications like pancreatitis and cardiovascular disease²^,³. Early genetic diagnosis facilitates targeted management and family counseling.

Conclusion: This report underscores the importance of early recognition and a multidisciplinary approach in managing severe neonatal hyperlipidemia due to GP1HBP1 mutations, optimizing outcomes in rare genetic dyslipidemias.

References: 1. Beigneux, A. P., et al. (2009). Mutations in the endothelial cell gene GPIHBP1 cause hyperlipoproteinemia type I. The Journal of Clinical Investigation, 119(5), 1258–1269. 2. Chait, A., & Eckel, R. H. (2019). Lipid management in pediatric patients with severe hyperlipidemia. Journal of Pediatric Endocrinology and Metabolism, 32(8), 725–733. 3. Young, S. G., et al. (2020). Molecular mechanisms of lipemia retinalis and therapeutic perspectives. Nature Reviews Endocrinology, 16(10), 569–581.