Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study

Abdurrahman Akgün; Gozde Uzunyayla; Neslihan Gucuyener Ozkan; Tanyel Zubarioglu; Meral Bahar İster; Özlem Ünal; Esra Er; Pelin Teke Kısa; Hüseyin Bilgin; Merve Aslantaş; Hasan Onal; Ertugrul Kiykim; Ayse Cigdem Aktuglu Zeybek

doi:10.5798/dicletip.1723050

Research Article

Year 2025, Volume: 52 Issue: 2, 283 - 297, 20.06.2025

Abdurrahman Akgün , Gozde Uzunyayla Neslihan Gucuyener Ozkan Tanyel Zubarioglu Meral Bahar İster Özlem Ünal , Esra Er , Pelin Teke Kısa , Hüseyin Bilgin , Merve Aslantaş , Hasan Onal , Ertugrul Kiykim Ayse Cigdem Aktuglu Zeybek

https://doi.org/10.5798/dicletip.1723050

Abstract

References

1.Wiegman A, Gidding SS, Watts GF, et al. Familialhypercholesterolaemia in children and adolescents:gaining decades of life by optimizing detection andtreatment. Eur Heart J. 2015;36(36):2425-37.doi:10.1093/eurheartj/ehv157
2.Ison HE, Clarke SL, Knowles JW. FamilialHypercholesterolemia Synonyms: FamilialHypercholesterolaemia, HyperlipoproteinemiaType IIA. In: Adam MP, Feldman J, Mirzaa GM, et al.,eds. GeneReviews® [Internet].; 2022. AccessedOctober 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK174884/
3.Maliachova O, Stabouli S. FamilialHypercholesterolemia in Children and Adolescents:Diagnosis and Treatment. Curr Pharm Des.2019;24(31):3672-3677.doi:10.2174/1381612824666181010145807
4.Singh S, Bittner V. FamilialHypercholesterolemia—Epidemiology, Diagnosis,and Screening. CurrAtheroscler Rep. 2015;17(2):3.doi:10.1007/s11883-014-0482-5
5.Cuchel M, Bruckert E, Ginsberg HN, et al.Homozygous familial hypercholesterolaemia: newinsights and guidance for clinicians to improvedetection and clinical management. A position paper from the Consensus Panel on FamilialHypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-57. doi:10.1093/eurheartj/ehu274
6.Harada-Shiba M, Ohtake A, Sugiyama D, et al.Guidelines for the Diagnosis and Treatment ofPediatric Familial Hypercholesterolemia 2022. JAtherosclerThromb. 2023;30(5):CR006.doi:10.5551/jat.CR006
7.Cohen H, Stefanutti C, Di Giacomo S, et al. CurrentApproach to the Diagnosis and Treatment ofHeterozygote and Homozygous FH Children andAdolescents. CurrAtheroscler Rep. 2021;23(6).doi:10.1007/s11883-021-00926-3
8.Du Z, Du Y, Li L, et al. Metabolomic Approach toScreening Homozygotes in Chinese Patients withSevere Familial Hypercholesterolemia. J Clin Med.2023;12(2):483. doi:10.3390/jcm12020483
9.Watts GF, Lewis B, Sullivan DR. Familialhypercholesterolemia: a missed opportunity inpreventive medicine. Nat ClinPractCardiovasc Med.2007;4(8):404-405. doi:10.1038/ncpcardio0941
10.Widhalm K, Binder CB, Kreissl A, et al. Suddendeath in a 4-year-old boy: a near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) inhomozygous familial hypercholesterolemia. JPediatr. 2011;158(1):167.doi:10.1016/j.jpeds.2010.06.027
11.Gautschi M, Pavlovic M, Nuoffer JM. Fatalmyocardial infarction at 4.5 years in a case ofhomozygous familial hypercholesterolaemia. JIMDRep. 2012;2:45-50. doi:10.1007/8904_2011_45
12.Pederiva C, Gazzotti M, Arca M, et al. ClinicalApproach in the Management of Paediatric Patientswith Familial Hypercholesterolemia: A NationalSurvey Conducted by the LIPIGEN Paediatric Group.Nutrients. 2023;15(15):3468.doi:10.3390/nu15153468
13.Sonmez A, Demirci I, Haymana C, et al. Clinicalcharacteristics of adult and paediatric patients withfamilial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.Atherosclerosis. 2023;375:9-20.doi:10.1016/j.atherosclerosis.2023.04.011
14.Brett T. Universal screening for familialhypercholesterolaemia in newborns: Time forgeneral practice to contribute. Aust J Gen Pract.2023;52(4):246-248. doi:10.31128/AJGP-10-22- 6581.
15.Feingold KR, Chait A. Approach to patients withelevated low-density lipoprotein cholesterol levels.Best Pract Res ClinEndocrinolMetab. Publishedonline May 1, 2022. doi:10.1016/j.beem.2022.101658
16.Bouhairie VE, Goldberg AC. FamilialHypercholesterolemia. CardiolClin. 2015;33(2):169-179. doi:10.1016/j.ccl.2015.01.001
17.Mansfield BS, Raal FJ. Regression of cutaneousxanthomata in patient with homozygous familialhypercholesterolemia using novel therapies. TheLancet. 2023;402(10404):e11. doi:10.1016/S0140-6736(23)01515-5
18.McGowan MP, Hosseini Dehkordi SH, MoriartyPM, Duell PB. Diagnosis and Treatment ofHeterozygous Familial Hypercholesterolemia. J AmHeart Assoc. 2019;8(24). doi:10.1161/JAHA.119.013225
19.Rutkowska L, Pinkier I, Sałacińska K, et al.Identification of New Copy Number Variation andthe Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial HypercholesterolemiaPatients. Genes (Basel). 2022;13(8):1424.doi:10.3390/genes13081424
20.Mytilinaiou M, Kyrou I, Khan M,Grammatopoulos DK, Randeva HS. FamilialHypercholesterolemia: New Horizons for Diagnosisand Effective Management. Front Pharmacol.2018;9. doi:10.3389/fphar.2018.00707
21.Turgeon RD, Barry AR, Pearson GJ. Familialhypercholesterolemia: Review of diagnosis,screening, and treatment. Can Fam Physician.2016;62(1):32-37.
22.Williams L, Wilson D. Nutritional management of pediatric dyslipidemia. Endotext MDText.com, Inc.Published online April 30, 2023.
23.Butt WZ, Yee JK. The Role of Non-statin Lipid-Lowering Medications in Youth with Hypercholesterolemia. CurrAtheroscler Rep. 2022;24(5):379-89. doi:10.1007/s11883-022-01013-x
24.Fachin A, De Carlo C, Maestro A, et al. RapidResolution ofLife-Threatening Hypertriglyceridemia after Evinacumab Administration in a Pediatric HSCT Recipient: A Case Report. Pharmaceuticals. 2023;16(8). doi:10.3390/ph16081069
25.Wiegman A, Greber-Platzer S, Ali S, et al.Evinacumab for Pediatric Patients WithHomozygous Familial Hypercholesterolemia.Circulation. Published online October 20, 2023.doi:10.1161/circulationaha.123.065529
26.Weintraub SF, Schillow JA, Azari BM, Hirsh BJ.Implementation of Novel Lipid Therapies in aRefractory Heterozygous FamilialHypercholesterolemia Patient With AtheroscleroticDisease. JACC Case Rep. 2022;4(20):1327-1330.doi:10.1016/j.jaccas.2022.06.021
27.Gokay S, Kendirci M, Kaynar L, et al. Long-termefficacy of lipoprotein apheresis in the managementof familial hypercholesterolaemia: Application oftwo different apheresis techniques in childhood.Transfusion and Apheresis Science.2016;54(2):282-8.doi:10.1016/j.transci.2015.10.015
28.Coker M, Ucar SK, Simsek DG, et al. Low densitylipoprotein apheresis in pediatric patients withhomozygous familial hypercholesterolemia. Therapeutic Apheresis and Dialysis. 2009;13(2):121-8.doi:10.1111/j.1744-9987.2009.00666.x
29.Ishigaki Y, Kawagishi N, Hasegawa Y, et al. LiverTransplantation for Homozygous FamilialHypercholesterolemia. J AtherosclerThromb.2019;26(2):121-7. doi:10.5551/jat.RV17029

Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study

Year 2025, Volume: 52 Issue: 2, 283 - 297, 20.06.2025

https://doi.org/10.5798/dicletip.1723050

Abstract

Aim: Familial hypercholesterolemia leads to the buildup of atherosclerotic plaques in the arteries, greatly elevating the risk of early-onset coronary heart disease. The objective of this study was to examine the clinical, laboratory, and genetic profiles of patients affected by familial hypercholesterolemia.
Methods: A retrospective review was performed on the demographic, clinical, biochemical and genotypic profiles of 124 individuals diagnosed with familial hypercholesterolemia.
Results: These cases from 6 centres comprised 50.8% males and 49.2% females. There was a history of hypercholesterolemia in the mothers of 43.5% of the cases and in the fathers of 53.2%. At the time of diagnosis, 81.5% of the cases had no complaints, 3.2% had skin lesions and 3.2% had weight gain complaints. Mutations were detected in the LDLR gene in 95.2% of the cases, in the APOE gene in 3.2% and in the APOB gene in 1.6%.
Conclusion: Familial hypercholesterolemia cases are still under-detected both in Türkiye and worldwide. Consequently, the prevention of coronary artery diseases caused by hypercholesterolemia is not feasible, underscoring the need for implementing more robust and widespread screening protocols.

Keywords

Familial hypercholesterolemia, LDL-cholesterol, Atherosclerosis, Lipoprotein apheresis

References

1.Wiegman A, Gidding SS, Watts GF, et al. Familialhypercholesterolaemia in children and adolescents:gaining decades of life by optimizing detection andtreatment. Eur Heart J. 2015;36(36):2425-37.doi:10.1093/eurheartj/ehv157
2.Ison HE, Clarke SL, Knowles JW. FamilialHypercholesterolemia Synonyms: FamilialHypercholesterolaemia, HyperlipoproteinemiaType IIA. In: Adam MP, Feldman J, Mirzaa GM, et al.,eds. GeneReviews® [Internet].; 2022. AccessedOctober 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK174884/
3.Maliachova O, Stabouli S. FamilialHypercholesterolemia in Children and Adolescents:Diagnosis and Treatment. Curr Pharm Des.2019;24(31):3672-3677.doi:10.2174/1381612824666181010145807
4.Singh S, Bittner V. FamilialHypercholesterolemia—Epidemiology, Diagnosis,and Screening. CurrAtheroscler Rep. 2015;17(2):3.doi:10.1007/s11883-014-0482-5
5.Cuchel M, Bruckert E, Ginsberg HN, et al.Homozygous familial hypercholesterolaemia: newinsights and guidance for clinicians to improvedetection and clinical management. A position paper from the Consensus Panel on FamilialHypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-57. doi:10.1093/eurheartj/ehu274
6.Harada-Shiba M, Ohtake A, Sugiyama D, et al.Guidelines for the Diagnosis and Treatment ofPediatric Familial Hypercholesterolemia 2022. JAtherosclerThromb. 2023;30(5):CR006.doi:10.5551/jat.CR006
7.Cohen H, Stefanutti C, Di Giacomo S, et al. CurrentApproach to the Diagnosis and Treatment ofHeterozygote and Homozygous FH Children andAdolescents. CurrAtheroscler Rep. 2021;23(6).doi:10.1007/s11883-021-00926-3
8.Du Z, Du Y, Li L, et al. Metabolomic Approach toScreening Homozygotes in Chinese Patients withSevere Familial Hypercholesterolemia. J Clin Med.2023;12(2):483. doi:10.3390/jcm12020483
9.Watts GF, Lewis B, Sullivan DR. Familialhypercholesterolemia: a missed opportunity inpreventive medicine. Nat ClinPractCardiovasc Med.2007;4(8):404-405. doi:10.1038/ncpcardio0941
10.Widhalm K, Binder CB, Kreissl A, et al. Suddendeath in a 4-year-old boy: a near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) inhomozygous familial hypercholesterolemia. JPediatr. 2011;158(1):167.doi:10.1016/j.jpeds.2010.06.027
11.Gautschi M, Pavlovic M, Nuoffer JM. Fatalmyocardial infarction at 4.5 years in a case ofhomozygous familial hypercholesterolaemia. JIMDRep. 2012;2:45-50. doi:10.1007/8904_2011_45
12.Pederiva C, Gazzotti M, Arca M, et al. ClinicalApproach in the Management of Paediatric Patientswith Familial Hypercholesterolemia: A NationalSurvey Conducted by the LIPIGEN Paediatric Group.Nutrients. 2023;15(15):3468.doi:10.3390/nu15153468
13.Sonmez A, Demirci I, Haymana C, et al. Clinicalcharacteristics of adult and paediatric patients withfamilial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.Atherosclerosis. 2023;375:9-20.doi:10.1016/j.atherosclerosis.2023.04.011
14.Brett T. Universal screening for familialhypercholesterolaemia in newborns: Time forgeneral practice to contribute. Aust J Gen Pract.2023;52(4):246-248. doi:10.31128/AJGP-10-22- 6581.
15.Feingold KR, Chait A. Approach to patients withelevated low-density lipoprotein cholesterol levels.Best Pract Res ClinEndocrinolMetab. Publishedonline May 1, 2022. doi:10.1016/j.beem.2022.101658
16.Bouhairie VE, Goldberg AC. FamilialHypercholesterolemia. CardiolClin. 2015;33(2):169-179. doi:10.1016/j.ccl.2015.01.001
17.Mansfield BS, Raal FJ. Regression of cutaneousxanthomata in patient with homozygous familialhypercholesterolemia using novel therapies. TheLancet. 2023;402(10404):e11. doi:10.1016/S0140-6736(23)01515-5
18.McGowan MP, Hosseini Dehkordi SH, MoriartyPM, Duell PB. Diagnosis and Treatment ofHeterozygous Familial Hypercholesterolemia. J AmHeart Assoc. 2019;8(24). doi:10.1161/JAHA.119.013225
19.Rutkowska L, Pinkier I, Sałacińska K, et al.Identification of New Copy Number Variation andthe Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial HypercholesterolemiaPatients. Genes (Basel). 2022;13(8):1424.doi:10.3390/genes13081424
20.Mytilinaiou M, Kyrou I, Khan M,Grammatopoulos DK, Randeva HS. FamilialHypercholesterolemia: New Horizons for Diagnosisand Effective Management. Front Pharmacol.2018;9. doi:10.3389/fphar.2018.00707
21.Turgeon RD, Barry AR, Pearson GJ. Familialhypercholesterolemia: Review of diagnosis,screening, and treatment. Can Fam Physician.2016;62(1):32-37.
22.Williams L, Wilson D. Nutritional management of pediatric dyslipidemia. Endotext MDText.com, Inc.Published online April 30, 2023.
23.Butt WZ, Yee JK. The Role of Non-statin Lipid-Lowering Medications in Youth with Hypercholesterolemia. CurrAtheroscler Rep. 2022;24(5):379-89. doi:10.1007/s11883-022-01013-x
24.Fachin A, De Carlo C, Maestro A, et al. RapidResolution ofLife-Threatening Hypertriglyceridemia after Evinacumab Administration in a Pediatric HSCT Recipient: A Case Report. Pharmaceuticals. 2023;16(8). doi:10.3390/ph16081069
25.Wiegman A, Greber-Platzer S, Ali S, et al.Evinacumab for Pediatric Patients WithHomozygous Familial Hypercholesterolemia.Circulation. Published online October 20, 2023.doi:10.1161/circulationaha.123.065529
26.Weintraub SF, Schillow JA, Azari BM, Hirsh BJ.Implementation of Novel Lipid Therapies in aRefractory Heterozygous FamilialHypercholesterolemia Patient With AtheroscleroticDisease. JACC Case Rep. 2022;4(20):1327-1330.doi:10.1016/j.jaccas.2022.06.021
27.Gokay S, Kendirci M, Kaynar L, et al. Long-termefficacy of lipoprotein apheresis in the managementof familial hypercholesterolaemia: Application oftwo different apheresis techniques in childhood.Transfusion and Apheresis Science.2016;54(2):282-8.doi:10.1016/j.transci.2015.10.015
28.Coker M, Ucar SK, Simsek DG, et al. Low densitylipoprotein apheresis in pediatric patients withhomozygous familial hypercholesterolemia. Therapeutic Apheresis and Dialysis. 2009;13(2):121-8.doi:10.1111/j.1744-9987.2009.00666.x
29.Ishigaki Y, Kawagishi N, Hasegawa Y, et al. LiverTransplantation for Homozygous FamilialHypercholesterolemia. J AtherosclerThromb.2019;26(2):121-7. doi:10.5551/jat.RV17029

There are 29 citations in total.

Details

Primary Language	English
Subjects	Medical Education, Health Services and Systems (Other)
Journal Section	Original Articles
Authors	Abdurrahman Akgün Gozde Uzunyayla Neslihan Gucuyener Ozkan Tanyel Zubarioglu Meral Bahar İster Özlem Ünal Esra Er Pelin Teke Kısa Hüseyin Bilgin Merve Aslantaş Hasan Onal Ertugrul Kiykim Ayse Cigdem Aktuglu Zeybek
Publication Date	June 20, 2025
Submission Date	January 16, 2025
Acceptance Date	May 21, 2025
Published in Issue	Year 2025 Volume: 52 Issue: 2

Cite

APA	Akgün, A., Uzunyayla, G., Gucuyener Ozkan, N., Zubarioglu, T., et al. (2025). Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study. Dicle Medical Journal, 52(2), 283-297. https://doi.org/10.5798/dicletip.1723050
AMA	Akgün A, Uzunyayla G, Gucuyener Ozkan N, Zubarioglu T, İster MB, Ünal Ö, Er E, Teke Kısa P, Bilgin H, Aslantaş M, Onal H, Kiykim E, Aktuglu Zeybek AC. Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study. diclemedj. June 2025;52(2):283-297. doi:10.5798/dicletip.1723050
Chicago	Akgün, Abdurrahman, Gozde Uzunyayla, Neslihan Gucuyener Ozkan, Tanyel Zubarioglu, Meral Bahar İster, Özlem Ünal, Esra Er, Pelin Teke Kısa, Hüseyin Bilgin, Merve Aslantaş, Hasan Onal, Ertugrul Kiykim, and Ayse Cigdem Aktuglu Zeybek. “Clinical and Laboratory Evaluation of Cases With Familial Hypercholesterolemia: A Multicentre Study”. Dicle Medical Journal 52, no. 2 (June 2025): 283-97. https://doi.org/10.5798/dicletip.1723050.
EndNote	Akgün A, Uzunyayla G, Gucuyener Ozkan N, Zubarioglu T, İster MB, Ünal Ö, Er E, Teke Kısa P, Bilgin H, Aslantaş M, Onal H, Kiykim E, Aktuglu Zeybek AC (June 1, 2025) Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study. Dicle Medical Journal 52 2 283–297.
IEEE	A. Akgün, “Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study”, diclemedj, vol. 52, no. 2, pp. 283–297, 2025, doi: 10.5798/dicletip.1723050.
ISNAD	Akgün, Abdurrahman et al. “Clinical and Laboratory Evaluation of Cases With Familial Hypercholesterolemia: A Multicentre Study”. Dicle Medical Journal 52/2 (June 2025), 283-297. https://doi.org/10.5798/dicletip.1723050.
JAMA	Akgün A, Uzunyayla G, Gucuyener Ozkan N, Zubarioglu T, İster MB, Ünal Ö, Er E, Teke Kısa P, Bilgin H, Aslantaş M, Onal H, Kiykim E, Aktuglu Zeybek AC. Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study. diclemedj. 2025;52:283–297.
MLA	Akgün, Abdurrahman et al. “Clinical and Laboratory Evaluation of Cases With Familial Hypercholesterolemia: A Multicentre Study”. Dicle Medical Journal, vol. 52, no. 2, 2025, pp. 283-97, doi:10.5798/dicletip.1723050.
Vancouver	Akgün A, Uzunyayla G, Gucuyener Ozkan N, Zubarioglu T, İster MB, Ünal Ö, Er E, Teke Kısa P, Bilgin H, Aslantaş M, Onal H, Kiykim E, Aktuglu Zeybek AC. Clinical and Laboratory Evaluation of Cases with Familial Hypercholesterolemia: A Multicentre Study. diclemedj. 2025;52(2):283-97.

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