Internal Medicine Resident Womack Army Medical Center Fayetteville, North Carolina, United States
Introduction : Familial chylomicronemia syndrome (FCS) is an autosomal recessive disease with a prevalence of 1 in 1 million people caused by loss-of-function mutations involving the lipoprotein lipase (LPL) enzyme. FCS usually results from homozygous or compound heterozygous mutations of the LPL gene. Other etiologies include loss-of-function mutations in genes related to the regulation of LPL. LPL enzyme impairment results in decreased clearance of triglyceride-rich lipoproteins (TRL) and hypertriglyceridemia (HTG). Clinical signs and symptoms include eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, and recurrent acute pancreatitis (AP). Diagnosis of FCS uses personal and family history, signs and symptoms, and lab findings, which include early onset of symptoms, recurrent abdominal pain, AP, fasting HTG, absence of secondary causes of HTG, and genetic testing. Treatment involves management of co-morbid conditions, cessation of alcohol, removal or reduction of aggravating medications, and dietary fat restriction. Persons with FCS respond poorly to pharmacologic therapy for HTG.
Case(s) Description : A 47-year-old male initially presented after his brother was diagnosed with HTG in 2007. Subsequent testing revealed a triglyceride (TG) level of 3046 mg dL-1. His HTG was treated with rosuvastatin and fenofibrate but was refractory to pharmacologic therapy. His TGs remained elevated and were >4000 mg dL-1 in 2017. He had a complex course with manifestations of FCS, including recurrent AP complicated by pancreatogenic diabetes mellitus as well as coronary artery disease requiring percutaneous intervention. TG levels have responded best to dietary changes, though they remain elevated. Based on his refractory severe HTG, recurrent AP, and family history of HTG, the patient was diagnosed with FCS in 2019. Genetic testing performed in 2019 and repeated in 2023 was negative for known genetic mutations, including APOA5, APOC2, CREB3L3, GPD1, GPIHBP1, LCAT, LIPA, LIPC, LMF1, LPL, and LRP6.
Discussion : FCS is an autosomal recessive disease of chylomicron metabolism characterized by HTG and serious complications such as AP. Despite negative genetic testing, this patient carries a diagnosis of FCS based on his family history, clinical presentation, and lab findings. We do not currently have effective therapies to reduce complications and improve quality of life in patients with FCS. This case suggests the existence of unknown genes or new mutations of known genes that may be future targets for novel therapies. This case highlights a rare condition that clinicians should be aware of and the need for future research and development of therapeutics, given the high morbidity and mortality in this population.
