Advances in diagnosis and potential therapeutic options for familial chylomicronemia syndrome

ABSTRACT

Introduction: Familial chylomicronemia syndrome (FCS) is a rare disorder in which there is a lack of chylomicron clearance from the plasma leading to severe hypertriglyceridemia. This is classically due to deficiency in lipoprotein lipase or one of its cofactors. There are many complications, including recurrent bouts of triglyceride-induced pancreatitis.

Areas covered: Underlying genetic causes of FCS are reviewed, including discussion of monogenic versus polygenic forms. The complications, goals of treatment, currently available treatments and future treatments are discussed. A case of a male patient with polygenic FCS that includes heterozygous APOA5 deficiency is presented.

Expert opinion: Additional effective treatment options are needed given the significant morbidity associated with FCS. Therapies with the ability to dramatically lower triglycerides and the risk of acute pancreatitis exist, however are minimally available to FCS patients at this time. Volanesorsen is one such therapy; there is optimism that it will have approval in the United States, Canada and Europe for FCS in the near future. Polygenic forms of FCS should be recognized and included in trials investigating new therapies as these patients are likely to receive similar benefits as those with a monogenic etiology.

KEYWORDS:

• Familial chylomicronemia syndrome
• hypertriglyceridemia
• acute pancreatitis
• lipoprotein lipase deficiency
• future therapies
• polygenic

Article Highlights

• Familial chylomicronemia syndrome inflicts significant physical and psychological harm, with the greatest burden due to episodes of recurrent pancreatitis

• The diagnosis was previously restricted to monogenic FCS, caused by autosomal recessive deficiency in LPL or one of its cofactors. More recently, polygenic FCS has been recognized, which is due to heterozygous deficiency or no identified mutation in LPL or one of its cofactors.

• An example of polygenic FCS is provided detailing a man with partial apolipoprotein A5 deficiency.

• Available triglyceride-lowering medications offer little benefit in FCS, particularly monogenic FCS. Plasmapheresis is currently available and can be considered to treat some episodes of acute pancreatitis. It can potentially be used to prevent acute pancreatitis, however data are limited.

• Treatments have been developed that better target chylomicron metabolism, however the majority currently lack approval for FCS treatment.

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Declaration of interest

M Davidson has acted as consultant for Akcea. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper is not funded.