Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

MedGen UID:: 1653798
•Concept ID:: C4751204
•: Disease or Syndrome

Synonym:	hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency
SNOMED CT:	Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency (773726000)
Modes of inheritance:	Semidominant inheritance MedGen UID: 1693292 •Concept ID: C5139139 • Genetic Function Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on chromosomes in which a trait can manifest in a monoallelic (e.g. heterozygotes) and biallelic (e.g. homozygotes, compound heterozygotes) state, with similar or differing phenotype severity present dependent on the number of alleles affected. Semidominant inheritance (Orphanet)

Monarch Initiative:	MONDO:0016203
Orphanet:	ORPHA209902

Definition

A rare genetic sterol metabolism disorder characterised by increased LDL cholesterol serum levels (which are resistant to treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), hypertriglyceridaemia, and decreased rate of bile acid excretion, resulting from cholesterol 7alpha-hydroxylase deficiency. Premature gallstone disease and/or premature coronary and peripheral vascular disease are frequently associated. [from SNOMEDCT_US]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVHypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

Inborn disorder of bile acid synthesis
- Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

Professional guidelines

PubMed

Primary hypercholesterolemia: genetic causes and treatment of five monogenic disorders.

Pullinger CR, Kane JP, Malloy MJ
Expert Rev Cardiovasc Ther 2003 May;1(1):107-19. doi: 10.1586/14779072.1.1.107. PMID: 15030301

See all (1)

Recent clinical studies

Etiology

Lipoprotein-X fifty years after its original discovery.

Fellin R, Manzato E
Nutr Metab Cardiovasc Dis 2019 Jan;29(1):4-8. Epub 2018 Sep 26 doi: 10.1016/j.numecd.2018.09.006. PMID: 30503707

Vitamin D receptor activation down-regulates the small heterodimer partner and increases CYP7A1 to lower cholesterol.

Chow EC, Magomedova L, Quach HP, Patel R, Durk MR, Fan J, Maeng HJ, Irondi K, Anakk S, Moore DD, Cummins CL, Pang KS
Gastroenterology 2014 Apr;146(4):1048-59. Epub 2013 Dec 21 doi: 10.1053/j.gastro.2013.12.027. PMID: 24365583

Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435.

Bhat BG, Rapp SR, Beaudry JA, Napawan N, Butteiger DN, Hall KA, Null CL, Luo Y, Keller BT
J Lipid Res 2003 Sep;44(9):1614-21. Epub 2003 Jun 16 doi: 10.1194/jlr.M200469-JLR200. PMID: 12810816

See all (3)

Therapy

NPC1L1 Deficiency Suppresses Ileal Fibroblast Growth Factor 15 Expression and Increases Bile Acid Pool Size in High-Fat-Diet-Fed Mice.

Jia L, Ma Y, Haywood J, Jiang L, Xue B, Shi H, Dawson PA, Yu L
Cells 2021 Dec 9;10(12) doi: 10.3390/cells10123468. PMID: 34943976 Free PMC Article

The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors.

Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Müller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD
Mol Endocrinol 2007 Jul;21(7):1603-16. Epub 2007 Apr 24 doi: 10.1210/me.2007-0133. PMID: 17456796

Primary hypercholesterolemia: genetic causes and treatment of five monogenic disorders.

Pullinger CR, Kane JP, Malloy MJ
Expert Rev Cardiovasc Ther 2003 May;1(1):107-19. doi: 10.1586/14779072.1.1.107. PMID: 15030301

See all (3)

Prognosis

Lipoprotein-X fifty years after its original discovery.

Fellin R, Manzato E
Nutr Metab Cardiovasc Dis 2019 Jan;29(1):4-8. Epub 2018 Sep 26 doi: 10.1016/j.numecd.2018.09.006. PMID: 30503707

See all (1)

Clinical prediction guides

Lipoprotein-X fifty years after its original discovery.

Fellin R, Manzato E
Nutr Metab Cardiovasc Dis 2019 Jan;29(1):4-8. Epub 2018 Sep 26 doi: 10.1016/j.numecd.2018.09.006. PMID: 30503707

Alterations in gene expression in vitamin D-deficiency: Down-regulation of liver Cyp7a1 and renal Oat3 in mice.

Quach HP, Noh K, Hoi SY, Bruinsma A, Groothuis GMM, Li AP, Chow ECY, Pang KS
Biopharm Drug Dispos 2018 Feb;39(2):99-115. Epub 2018 Jan 30 doi: 10.1002/bdd.2118. PMID: 29243851

Vitamin D receptor activation down-regulates the small heterodimer partner and increases CYP7A1 to lower cholesterol.

Alterations in bile acid synthesis in carriers of hepatocyte nuclear factor 1α mutations.

Ekholm E, Nilsson R, Groop L, Pramfalk C
J Intern Med 2013 Sep;274(3):263-72. Epub 2013 May 6 doi: 10.1111/joim.12082. PMID: 23607861

The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors.

See all (5)