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Case Reports
. 2024 Jun 14;18(1):278.
doi: 10.1186/s13256-024-04532-0.

Monogenic hypertriglyceridemia and recurrent pancreatitis in a homozygous carrier of a rare APOA5 mutation: a case report

Umidakhon Makhmudova  1   2   3   4 , P Christian Schulze  5 , Stefan Lorkowski  6   7 , Winfried März  8 , J-A Geiling  5 , Oliver Weingärtner  5
Affiliations
Case Reports

Monogenic hypertriglyceridemia and recurrent pancreatitis in a homozygous carrier of a rare APOA5 mutation: a case report

Umidakhon Makhmudova et al. J Med Case Rep. .

Abstract

Background: Homozygous mutations in the APOA5 gene constitute a rare cause of monogenic hypertriglyceridemia, or familial chylomicronemia syndrome (FCS). We searched PubMed and identified 16 cases of homozygous mutations in the APOA5 gene. Severe hypertriglyceridemia related to monogenic mutations in triglyceride-regulating genes can cause recurrent acute pancreatitis. Standard therapeutic approaches for managing this condition typically include dietary interventions, fibrates, and omega-3-fatty acids. A novel therapeutic approach, antisense oligonucleotide volanesorsen is approved for use in patients with FCS.

Case presentation: We report a case of a 25-years old Afghani male presenting with acute pancreatitis due to severe hypertriglyceridemia up to 29.8 mmol/L caused by homozygosity in APOA5 (c.427delC, p.Arg143Alafs*57). A low-fat diet enriched with medium-chain TG (MCT) oil and fibrate therapy did not prevent recurrent relapses, and volanesorsen was initiated. Volanesorsen resulted in almost normalized triglyceride levels. No further relapses of acute pancreatitis occurred. Patient reported an improve life quality due to alleviated chronic abdominal pain and headaches.

Conclusions: Our case reports a rare yet potentially life-threatening condition-monogenic hypertriglyceridemia-induced acute pancreatitis. The implementation of the antisense drug volanesorsen resulted in improved triglyceride levels, alleviated symptoms, and enhanced the quality of life.

Keywords: APOA5; Acute pancreatitis; Case report; Monogenic hypertriglyceridemia; Volanesorsen.

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Conflict of interest statement

UM reports no conflict of interest regarding this article. WM reports grants and personal fees from Abbott Diagnostics, AMGEN, AMRYT, Boehringer Ingelheim, Sanofi, grants from Immundiagnostik GmbH, Novartis Pharma GmbH, personal fees from Vifor Pharma, and is employed with SYNLAB Holding Deutschland GmbH, outside the submitted work. OW received personal fees from AMGEN, Novartis, Sanofi, Berlin-Chemie, Sandoz, Amarin, Daiichi-Sankyo, Pfizer, Akcea Therapeutics and Sobi.

Figures

Fig. 1
Fig. 1
Triglyceride levels dynamics. After the therapy initiation, triglyceride levels improved and remained between 8 and 11 mmol/L, until May 2022, when a new episode of acute pancreatitis occurred. Volanesorsen was started shortly afterwards and results in the normalization and stabilization of triglyceride levels
Fig. 2
Fig. 2
triglyceride levels and platelet count after initiation of volanesorsen therapy. Following the start of volanesorsen therapy, platelet count and triglyceride levels were monitored. Volanesorsen treatment commenced shortly after a hospitalization due to acute pancreatitis, during which triglyceride levels peaked at approximately 18 mmol/L. Prior to discharge, triglyceride levels returned to normal, and volanesorsen therapy was initiated. Three weeks into the treatment, the platelet count decreased to 114,000/µl, prompting a switch to biweekly volanesorsen administration. This modified regimen led to the normalization of platelet count, maintaining stability at over 125,000/µl, alongside consistent triglyceride levels
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