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Homozygous familial hypercholesterolemia

MedGen UID:
575266
•Concept ID:
C0342881
•
Disease or Syndrome
Synonym: Familial hypercholesterolemia - homozygous
SNOMED CT: Familial homozygous hypercholesterolemia (238078005); Familial hypercholesterolemia - homozygous (238078005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
 
Monarch Initiative: MONDO:0018328
Orphanet: ORPHA391665

Definition

A rare disorder of lipid metabolism characterized by severely elevated low-density lipoprotein cholesterol levels and subsequent premature formation of atherosclerotic plaques in the coronary arteries, proximal aorta, and other arteries, significantly increasing the risk of cardiovascular disease at an early age. Xanthomas of the skin and in tendons are also a hallmark of the disease. Lethality is high due to early complications, in particular myocardial infarction. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHomozygous familial hypercholesterolemia

Professional guidelines

PubMed

Dyslipidemia Management in Pregnancy: Why Is It not Covered in the Guidelines?
Lewek J, Banach M
Curr Atheroscler Rep 2022 Jul;24(7):547-556. Epub 2022 Apr 30 doi: 10.1007/s11883-022-01030-w. PMID: 35499807
Dyslipidemia management update.
Chang Y, Robidoux J
Curr Opin Pharmacol 2017 Apr;33:47-55. Epub 2017 May 17 doi: 10.1016/j.coph.2017.04.005. PMID: 28527325
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE.
Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, Grunberger G, Guerin CK, Bell DSH, Mechanick JI, Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson M
Endocr Pract 2017 Apr;23(Suppl 2):1-87. doi: 10.4158/EP171764.APPGL. PMID: 28437620

Curated

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APOB, LDLR, PCSK9 Pathogenic Variants (Familial Hypercholesterolemia), 2019

The Cardiac Society of Australia and New Zealand, Diagnosis and Management of Familial Hypercholesterolaemia – Position Statement

Recent clinical studies

Etiology

Dyslipidemia Management in Pregnancy: Why Is It not Covered in the Guidelines?
Lewek J, Banach M
Curr Atheroscler Rep 2022 Jul;24(7):547-556. Epub 2022 Apr 30 doi: 10.1007/s11883-022-01030-w. PMID: 35499807
Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study.
Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel M; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators
Lancet 2022 Feb 19;399(10326):719-728. Epub 2022 Jan 28 doi: 10.1016/S0140-6736(21)02001-8. PMID: 35101175Free PMC Article
Lipid Disorders in Pregnancy.
Liberis A, Petousis S, Tsikouras P
Curr Pharm Des 2021;27(36):3804-3807. doi: 10.2174/1381612827666210421103245. PMID: 33882801
Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features.
Bertolini S, Calandra S, Arca M, Averna M, Catapano AL, Tarugi P; Italian Study Group of Homozygous Familial Hypercholesterolemia
Atherosclerosis 2020 Nov;312:72-78. Epub 2020 Sep 9 doi: 10.1016/j.atherosclerosis.2020.08.027. PMID: 32977124
Evinacumab for Homozygous Familial Hypercholesterolemia.
Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators
N Engl J Med 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215. PMID: 32813947

Diagnosis

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.
Cuchel M, Raal FJ, Hegele RA, Al-Rasadi K, Arca M, Averna M, Bruckert E, Freiberger T, Gaudet D, Harada-Shiba M, Hudgins LC, Kayikcioglu M, Masana L, Parhofer KG, Roeters van Lennep JE, Santos RD, Stroes ESG, Watts GF, Wiegman A, Stock JK, Tokgözoğlu LS, Catapano AL, Ray KK
Eur Heart J 2023 Jul 1;44(25):2277-2291. doi: 10.1093/eurheartj/ehad197. PMID: 37130090Free PMC Article
Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study.
Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel M; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators
Lancet 2022 Feb 19;399(10326):719-728. Epub 2022 Jan 28 doi: 10.1016/S0140-6736(21)02001-8. PMID: 35101175Free PMC Article
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Di Taranto MD, Giacobbe C, Palma D, Iannuzzo G, Gentile M, Calcaterra I, Guardamagna O, Auricchio R, Di Minno MND, Fortunato G
Clin Genet 2021 Nov;100(5):529-541. Epub 2021 Aug 3 doi: 10.1111/cge.14036. PMID: 34297352Free PMC Article
Homozygous Familial Hypercholesterolemia.
Nohara A, Tada H, Ogura M, Okazaki S, Ono K, Shimano H, Daida H, Dobashi K, Hayashi T, Hori M, Matsuki K, Minamino T, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):665-678. Epub 2021 Apr 18 doi: 10.5551/jat.RV17050. PMID: 33867421Free PMC Article
Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features.
Bertolini S, Calandra S, Arca M, Averna M, Catapano AL, Tarugi P; Italian Study Group of Homozygous Familial Hypercholesterolemia
Atherosclerosis 2020 Nov;312:72-78. Epub 2020 Sep 9 doi: 10.1016/j.atherosclerosis.2020.08.027. PMID: 32977124

Therapy

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.
Cuchel M, Raal FJ, Hegele RA, Al-Rasadi K, Arca M, Averna M, Bruckert E, Freiberger T, Gaudet D, Harada-Shiba M, Hudgins LC, Kayikcioglu M, Masana L, Parhofer KG, Roeters van Lennep JE, Santos RD, Stroes ESG, Watts GF, Wiegman A, Stock JK, Tokgözoğlu LS, Catapano AL, Ray KK
Eur Heart J 2023 Jul 1;44(25):2277-2291. doi: 10.1093/eurheartj/ehad197. PMID: 37130090Free PMC Article
Chemistry, structure and function of approved oligonucleotide therapeutics.
Egli M, Manoharan M
Nucleic Acids Res 2023 Apr 11;51(6):2529-2573. doi: 10.1093/nar/gkad067. PMID: 36881759Free PMC Article
Dyslipidemia Management in Pregnancy: Why Is It not Covered in the Guidelines?
Lewek J, Banach M
Curr Atheroscler Rep 2022 Jul;24(7):547-556. Epub 2022 Apr 30 doi: 10.1007/s11883-022-01030-w. PMID: 35499807
Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study.
Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel M; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators
Lancet 2022 Feb 19;399(10326):719-728. Epub 2022 Jan 28 doi: 10.1016/S0140-6736(21)02001-8. PMID: 35101175Free PMC Article
Evinacumab for Homozygous Familial Hypercholesterolemia.
Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators
N Engl J Med 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215. PMID: 32813947

Prognosis

Sitosterolemia.
Tada H, Kojima N, Takamura M, Kawashiri MA
Adv Clin Chem 2022;110:145-169. Epub 2022 Aug 9 doi: 10.1016/bs.acc.2022.06.006. PMID: 36210074
Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study.
Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel M; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators
Lancet 2022 Feb 19;399(10326):719-728. Epub 2022 Jan 28 doi: 10.1016/S0140-6736(21)02001-8. PMID: 35101175Free PMC Article
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Di Taranto MD, Giacobbe C, Palma D, Iannuzzo G, Gentile M, Calcaterra I, Guardamagna O, Auricchio R, Di Minno MND, Fortunato G
Clin Genet 2021 Nov;100(5):529-541. Epub 2021 Aug 3 doi: 10.1111/cge.14036. PMID: 34297352Free PMC Article
Homozygous Familial Hypercholesterolemia.
Nohara A, Tada H, Ogura M, Okazaki S, Ono K, Shimano H, Daida H, Dobashi K, Hayashi T, Hori M, Matsuki K, Minamino T, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):665-678. Epub 2021 Apr 18 doi: 10.5551/jat.RV17050. PMID: 33867421Free PMC Article
Liver Transplantation for Homozygous Familial Hypercholesterolemia.
Ishigaki Y, Kawagishi N, Hasegawa Y, Sawada S, Katagiri H, Satomi S, Oikawa S
J Atheroscler Thromb 2019 Feb 1;26(2):121-127. Epub 2018 Dec 15 doi: 10.5551/jat.RV17029. PMID: 30555131Free PMC Article

Clinical prediction guides

Efficacy, Safety, and Tolerability of Inclisiran in Patients With Homozygous Familial Hypercholesterolemia: Results From the ORION-5 Randomized Clinical Trial.
Raal F, Durst R, Bi R, Talloczy Z, Maheux P, Lesogor A, Kastelein JJP; ORION-5 Study Investigators
Circulation 2024 Jan 30;149(5):354-362. Epub 2023 Oct 18 doi: 10.1161/CIRCULATIONAHA.122.063460. PMID: 37850379Free PMC Article
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Di Taranto MD, Giacobbe C, Palma D, Iannuzzo G, Gentile M, Calcaterra I, Guardamagna O, Auricchio R, Di Minno MND, Fortunato G
Clin Genet 2021 Nov;100(5):529-541. Epub 2021 Aug 3 doi: 10.1111/cge.14036. PMID: 34297352Free PMC Article
Lipid Disorders in Pregnancy.
Liberis A, Petousis S, Tsikouras P
Curr Pharm Des 2021;27(36):3804-3807. doi: 10.2174/1381612827666210421103245. PMID: 33882801
Homozygous Familial Hypercholesterolemia.
Nohara A, Tada H, Ogura M, Okazaki S, Ono K, Shimano H, Daida H, Dobashi K, Hayashi T, Hori M, Matsuki K, Minamino T, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):665-678. Epub 2021 Apr 18 doi: 10.5551/jat.RV17050. PMID: 33867421Free PMC Article
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE.
Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, Grunberger G, Guerin CK, Bell DSH, Mechanick JI, Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson M
Endocr Pract 2017 Apr;23(Suppl 2):1-87. doi: 10.4158/EP171764.APPGL. PMID: 28437620

Recent systematic reviews

Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century.
Bélanger AM, Akioyamen LE, Ruel I, Hales L, Genest J
Eur Heart J 2022 Sep 7;43(34):3227-3239. doi: 10.1093/eurheartj/ehac339. PMID: 35776569
Health-related quality of life in homozygous familial hypercholesterolemia: A systematic review and meta-analysis.
Alothman L, Bélanger AM, Ruel I, Brunham LR, Hales L, Genest J, Akioyamen LE
J Clin Lipidol 2022 Jan-Feb;16(1):52-65. Epub 2021 Dec 6 doi: 10.1016/j.jacl.2021.11.014. PMID: 35027327
Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis.
Kramer AI, Akioyamen LE, Lee S, Bélanger A, Ruel I, Hales L, Genest J, Brunham LR
Eur J Prev Cardiol 2022 May 5;29(5):817-828. doi: 10.1093/eurjpc/zwab224. PMID: 34957506
Efficacy and safety of lipoprotein apheresis in children with homozygous familial hypercholesterolemia: A systematic review.
Luirink IK, Determeijer J, Hutten BA, Wiegman A, Bruckert E, Schmitt CP, Groothoff JW
J Clin Lipidol 2019 Jan-Feb;13(1):31-39. Epub 2018 Nov 3 doi: 10.1016/j.jacl.2018.10.011. PMID: 30553758
The panorama of familial hypercholesterolemia in Latin America: a systematic review.
Mehta R, Zubirán R, Martagón AJ, Vazquez-Cárdenas A, Segura-Kato Y, Tusié-Luna MT, Aguilar-Salinas CA
J Lipid Res 2016 Dec;57(12):2115-2129. Epub 2016 Oct 24 doi: 10.1194/jlr.R072231. PMID: 27777316Free PMC Article

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    Practice guidelines

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APOB, LDLR, PCSK9 Pathogenic Variants (Familial Hypercholesterolemia), 2019
    • CSANZ, 2016
      The Cardiac Society of Australia and New Zealand, Diagnosis and Management of Familial Hypercholesterolaemia – Position Statement

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • PMC Articles
      Related information in PubMed Central Links
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