Diagnostic and Therapeutic Challenges of Homozygous and Severe Heterozygous Familial Hypercholesterolemia from Clinical Aspect—A Single-Center Study

Background/Objectives: The clinical presentation of homozygous familial hypercholesterolemia (HoFH) and severe heterozygous familial hypercholesterolemia (sHeFH) often demonstrates substantial overlap, as low-density lipoprotein cholesterol (LDL-C) levels may fall within similar ranges in both conditions. Methods: In this single-center 10-year retrospective study at the University of Debrecen, Hungary, we present the clinical characteristics of patients with 6 HoFH and 6 sHeFH diagnosed by genetic testing, discuss the diagnostic limitations encountered in clinical practice, and outline the key components of therapeutic management. Results: The mean age at diagnosis was lower in the HoFH group (31.83 ± 19.5 vs. 41.83 ± 15.9 years). The differences in total cholesterol (13.48 ± 7.4 vs. 11.02 ± 3.5 mmol/L) and LDL-C levels (10.89 ± 6.6 vs. 8.58 ± 3.26 mmol/L) between the groups were not statistically significant. Interestingly, vascular complications were more frequent in sHeFH group as well (4 vs. 1 patients). In neither the HoFH nor the sHeFH group were we able to achieve the target LDL-C levels, due in part to the specific features of the reimbursement system, patient and parental preferences, the extremely high baseline LDL-C levels, and certain genetic characteristics. Conclusions: Our findings highlight the importance of genetic testing-based personalized therapy in these specific patient subpopulations. We emphasize that serum LDL-C alone is insufficient to distinguish between HoFH and sHeFH patients, and that therapeutic challenges should be anticipated in both groups arising partly from limited patient adherence as well as from financial constraints.