A Rare Encounter: Familial Lipoprotein Lipase Deficiency in Pregnancy - Case Review and Emerging Therapies for Familial Chylomicronemia Syndrome

Background/Synopsis

Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder affecting chylomicron metabolism, resulting in severe hypertriglyceridemia (sHTG) associated with recurrent acute pancreatitis (AP). We present a case of young woman with a rare instance of familial lipoprotein lipase (LPL) deficiency during pregnancy.

Objective/Purpose

Despite that FCS is associated with poor quality of life and increased lifelong risk of sHTG and AP, there is lack of awareness about the disease. We aim to describe clinical features and complications associated with FCS, with the overarching objective of enhancing awareness regarding this condition. Additionally, we explore emerging therapies for the treatment of sHTG.

Methods

Literature review and retrospective review of electronic health records were performed.

Results

17-year-old Guatemalan female at 25 weeks gestation presented with acute abdominal pain and was found to have a lipase of 4076 mg/dL, amylase of 860 mg/dL and triglyceride (TG) level of 2233 mg/dL requiring apheresis for sHTG induced AP. She re-presented multiple times with sHTG and required treatment for recurrent AP. Genetic testing showed homozygous LPL gene mutation involving novel early truncation and ABCA1 transporter heterozygosity linked to reduced HDL levels. Patient continues to experience a sequela of complications despite treatment with fibrates, statins, omega-3-acid ethyl esters and a low-fat diet.

Conclusions

There are currently no treatments for FCS except for lifelong fat restrictive diet. Orlistat, a gastric and pancreatic lipase inhibitor has shown some promise in terms of reducing TG levels. Prior therapies have targeted various phenotypes of sHTG in familial combined hyperlipidemia syndromes with off-label use in FCS. More recently, targeted pharmacotherapies for FCS including apoC-III hepatocyte-directed antisense oligonucleotide such as Volanesorsen (approved in Europe) and Olezarsen (currently in phase-3 trial) have shown promise. Preliminary results from the CORE trials have shown significant reduction in TG levels in FCS patients and 100% reduction in AP. Additionally, small interfering ribonucleic acid (siRNA) based therapies are being studied in patients with FCS.

Albeit a rare genetic disorder, FCS should be suspected in patients with sHTG in the absence of secondary causes and should be referred to lipid specialists for further management. FCS in pregnancy can pose even more challenges given increased insulin resistance and fetal and maternal burden of disease. Trials for novel targeted therapies have shown encouraging results and may help reduce ASCVD risk and complications associated with FCS.