CASE REPORT article
Front. Cardiovasc. Med.
Sec. Lipids in Cardiovascular Disease
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1643771
Beating the Assumed Prognosis: Homozygous Familial Hypercholesterolemia with Unexpected Long Survival
Provisionally accepted
- 1Vseobecna fakultni nemocnice v Praze, Prague, Czechia
- 2Institute for Clinical and Experimental Medicine (IKEM), Prague, Czechia
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Background: Familial hypercholesterolemia (FH) is a common autosomal codominant genetic disorder, with heterozygous FH (HeFH) affecting approximately 1 in 310 individuals. FH is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which are typically twice those of unaffected individuals, and by a markedly increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Homozygous FH (HoFH) is rarer and presents substantial phenotypic variability, with total cholesterol levels ranging from 13 to 55 mmol/L. Case Presentations: We report three atypical cases of HoFH, with one patient being a homozygote for the c.1775G>A (p.Gly592Glu) variant and two patients being compound heterozygotes (c.340T>A/c.1775G>A, p.Phe114Ile/p.Gly592Glu and c.761A>C/c.910G>A, p.Gln254Pro/p.Asp304Tyr). All the patients presented with relatively mild clinical phenotypes, delayed diagnoses, and no evidence of early-onset ASCVD. Conclusions: These cases underscore the clinical heterogeneity of HoFH and challenge the prevailing assumption that HoFH uniformly results in severe cardiovascular outcomes. Personalized treatment strategies are essential for improving prognoses and quality of life of affected individuals.
Keywords: Familial Hypercholesterolemia, homozygous, phenotypic variability, Treatment, Longevity
Received: 09 Jun 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Zlatohlavek, Beňová Becherová, Foglarova, Dudkova and Hubacek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lukas Zlatohlavek, lukas.zlatohlavek@lf1.cuni.cz
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