A Novel APOC2 Missense Mutation Causing Apolipoprotein C-II Deficiency With Severe Triglyceridemia and Pancreatitis.

Abstract

Context:

Familial chylomicronemia syndrome (FCS) is a rare heritable disorder associated with severe hypertriglyceridemia and recurrent pancreatitis. Lipoprotein lipase deficiency and apolipoprotein C-II deficiency are two well-characterized autosomal recessive causes of FCS, and three other genes have been described to cause FCS. Because therapeutic approaches can vary according to the underlying etiology, it is important to establish the molecular etiology of FCS.

Case Description:

A man originally from North Africa was referred to the University of Pennsylvania Lipid Clinic for severe hypertriglyceridemia and recurrent pancreatitis, consistent with the clinical diagnosis of FCS. Molecular analyses of FCS-associated genes revealed a homozygous missense variant R72T in APOC2. Molecular modeling of the variant predicted that the apolipoprotein C-II R72T peptide has reduced lipid binding affinity. In vitro studies of the patient's plasma confirmed the lack of functional apoC-II activity. Moreover, the apoC-II protein was undetectable in the patient's plasma, quantitatively as well as qualitatively.

Conclusions:

We identified a missense APOC2 variant causing apoC-II deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis. Beyond dietary management and usual pharmacologic therapies, an apoC-II mimetic peptide may become an optional therapy in patients with apoC-II deficiency in the future.

• Authors: Masako Ueda, Richard L Dunbar, Anna Wolska, Tracey U Sikora, Maria Del Rosario Escobar, Naomi Seliktar, Emil deGoma, Stephanie DerOhannessian, Linda Morrell, Adam D McIntyre, Frances Burke, Denis Sviridov, Marcelo Amar, Robert D Shamburek, Lita Freeman, Robert A Hegele, Alan T Remaley, Daniel J Rader
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 5 Pg. 1454-1457 (05 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28201738 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• Apolipoprotein C-II

Topics

• Adult
• Apolipoprotein C-II (deficiency, genetics)
• Black People
• Homozygote
• Humans
• Hyperlipoproteinemia Type I (complications, genetics, metabolism)
• Hypertriglyceridemia (etiology, metabolism)
• Male
• Mutation, Missense
• Pancreatitis (etiology, metabolism)
• Recurrence