Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

Kamal, Aisyah; Kanchau, Johanes Dedi; Shahuri, Nur Syahirah; Mohamed-Yassin, Mohamed Syarif; Baharudin, Noorhida; Razak, Suraya Abdul; Badlishah-Sham, Siti Fatimah; Abdul-Hamid, Hasidah; Aziz, Aznida Firzah Abdul; Al-Khateeb, Alyaa; Chua, Yung An; Kasim, Noor Alicezah Mohd; Kadir, Siti Hamimah Sheikh Abdul; Nawawi, Hapizah; Qureshi, Nadeem; Ramli, Anis Safura

Abstract

BACKGROUND: In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care.

CASE REPORT: In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing.

CONCLUSIONS: This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

• Journal Article Type: Article
• Acceptance Date: Feb 21, 2023
• Online Publication Date: Mar 23, 2023
• Publication Date: Apr 27, 2023
• Deposit Date: May 11, 2023
• Publicly Available Date: May 11, 2023
• Journal: American Journal of Case Reports
• Electronic ISSN: 1941-5923
• Publisher: International Scientific Information, Inc.
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Article Number: e939489
• DOI: https://doi.org/10.12659/AJCR.939489
• Keywords: Atherosclerosis, Coronary Artery Disease, Hyperlipidemia with Familial Hypercholesterolemic Xanthomatosis, Physicians, Primary Care
• Public URL: https://nottingham-repository.worktribe.com/output/19454528
• Publisher URL: https://amjcaserep.com/abstract/full/idArt/939489