Treatment with the selective PPARα modulator pemafibrate and strict dietary fat restriction successfully maintained serum triglyceride levels below 500 mg/dL in a patient with familial chylomicronemia syndrome.
Case Report (n=1)
No
Does pemafibrate combined with dietary restriction reduce triglyceride levels in a patient with familial chylomicronemia syndrome caused by a novel GPIHBP1 mutation?
Pemafibrate combined with strict dietary fat restriction successfully managed severe hypertriglyceridemia in a rare case of FCS caused by a novel homozygous GPIHBP1 mutation.
Aim: Familial chylomicronemia syndrome (FCS) is a rare disorder characterized by the accumulation of chylomicrons in the circulation due to genetic defects or autoantibodies affecting lipoprotein lipase (LPL), the key enzyme responsible for the metabolism of chylomicrons and very-low-density lipoproteins (VLDL), or its associated proteins, including apolipoprotein (apo) C-II, apoA-V, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1). This condition is associated with markedly elevated serum triglyceride (TG) levels and, in severe cases, recurrent episodes of pancreatitis and eruptive xanthomas. Among these etiologies, genetic deficiency of GPIHBP1 is exceedingly rare. We aimed to clarify the clinical and genetic basis and treatment strategies of a patient with GPIHBP1 deficiency. Methods: A 47-year-old woman with a childhood diagnosis of FCS presented with severe epigastric pain and was admitted to Rinku General Medical Center for emergency management of acute pancreatitis secondary to severe chylomicronemia. She had a history of severe hypertriglyceridemia complicated by pancreatitis during her first pregnancy and extreme hypertriglyceridemia exceeding 6, 000 mg/dL during her second pregnancy without the development of pancreatitis. DNA sequence analysis was performed as a clinical diagnostic test and outsourced to KUBIX Inc. (Hakusan, Ishikawa, Japan). Results: Laboratory evaluation revealed marked hypertriglyceridemia (1, 262 mg/dL) with a type V hyperlipoproteinemia pattern. Serum preheparin LPL mass was markedly reduced, and circulating GPIHBP1 was undetectable. Genetic analysis identified a novel homozygous frameshift mutation in the GPIHBP1 gene (NM₁78172. 4: c. 20del p. Val7AlafsTer73), which has not been previously reported in public databases. No pathogenic variants were detected in other LPL-related genes. Acute pancreatitis improved rapidly with fasting and intravenous fluid therapy. Strict dietary fat restriction, followed by the addition of the selective PPARα modulator pemafibrate, successfully maintained TG levels below 500 mg/dL during follow-up. Conclusion: We report an extremely rare case of FCS caused by a novel homozygous mutation in the GPIHBP1 gene, in which pregnancy served as a major trigger for severe hypertriglyceridemia. Early diagnosis and strict lipid control are essential to prevent recurrent pancreatitis in patients with GPIHBP1 deficiency.
Otsuki et al. (Thu,) conducted a case report in Familial chylomicronemia syndrome (FCS) (n=1). Pemafibrate was evaluated on Serum triglyceride (TG) levels. Treatment with the selective PPARα modulator pemafibrate and strict dietary fat restriction successfully maintained serum triglyceride levels below 500 mg/dL in a patient with familial chylomicronemia syndrome.