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LCAT deficiency

MedGen UID:
9698
Concept ID:
C0023195
Disease or Syndrome
Synonyms: Lecithin Acyltransferase Deficiency; Lecithin Cholesterol Acyltransferase Deficiency
SNOMED CT: Familial lecithin cholesterol acyltransferase deficiency (1264565005); Complete LCAT deficiency (1264565005); Norum disease (1264565005); Complete LCAT (lecithin-cholesterol acyltransferase) deficiency (1264565005)
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).
 
Related gene: LCAT
 
Monarch Initiative: MONDO:0018999
OMIM®: 245900; 606967
Orphanet: ORPHA650

Definition

Lecithin:cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism and causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. [from OMIM]

Additional description

From MedlinePlus Genetics
Complete LCAT deficiency is a disorder that primarily affects the eyes and kidneys.

In complete LCAT deficiency, the clear front surface of the eyes (the corneas) gradually becomes cloudy. The cloudiness, which generally first appears in early childhood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As complete LCAT deficiency progresses, the corneal cloudiness worsens and can lead to severely impaired vision.

People with complete LCAT deficiency often have kidney disease that begins in adolescence or early adulthood. The kidney problems get worse over time and may eventually lead to kidney failure. Individuals with this disorder also usually have a condition known as hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Anemia can cause pale skin, weakness, fatigue, and more serious complications.

Other features of complete LCAT deficiency that occur in some affected individuals include enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy) or an accumulation of fatty deposits on the artery walls (atherosclerosis).  https://medlineplus.gov/genetics/condition/complete-lcat-deficiency

Professional guidelines

PubMed

Bonilha I, Luchiari B, Nadruz W, Sposito AC
Arch Endocrinol Metab 2023 Jan 18;67(1):3-18. doi: 10.20945/2359-3997000000585. PMID: 36651718Free PMC Article
Freeman LA, Shamburek RD, Sampson ML, Neufeld EB, Sato M, Karathanasis SK, Remaley AT
J Lipid Res 2019 May;60(5):1050-1057. Epub 2019 Feb 26 doi: 10.1194/jlr.D090233. PMID: 30808683Free PMC Article
Shamburek RD, Bakker-Arkema R, Auerbach BJ, Krause BR, Homan R, Amar MJ, Freeman LA, Remaley AT
J Clin Lipidol 2016 Mar-Apr;10(2):356-67. Epub 2015 Dec 23 doi: 10.1016/j.jacl.2015.12.007. PMID: 27055967Free PMC Article

Recent clinical studies

Etiology

Mehta R, Elías-López D, Martagón AJ, Pérez-Méndez OA, Sánchez MLO, Segura Y, Tusié MT, Aguilar-Salinas CA
Lipids Health Dis 2021 Jul 13;20(1):70. doi: 10.1186/s12944-021-01498-6. PMID: 34256778Free PMC Article
Kuroda M, Bujo H, Yokote K, Murano T, Yamaguchi T, Ogura M, Ikewaki K, Koseki M, Takeuchi Y, Nakatsuka A, Hori M, Matsuki K, Miida T, Yokoyama S, Wada J, Harada-Shiba M
J Atheroscler Thromb 2021 Jul 1;28(7):679-691. Epub 2021 Apr 18 doi: 10.5551/jat.RV17051. PMID: 33867422Free PMC Article
Pavanello C, Calabresi L
Curr Opin Lipidol 2020 Aug;31(4):232-237. doi: 10.1097/MOL.0000000000000697. PMID: 32618730
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
Ossoli A, Simonelli S, Vitali C, Franceschini G, Calabresi L
J Atheroscler Thromb 2016;23(2):119-27. Epub 2015 Nov 26 doi: 10.5551/jat.32854. PMID: 26607351

Diagnosis

Mehta R, Elías-López D, Martagón AJ, Pérez-Méndez OA, Sánchez MLO, Segura Y, Tusié MT, Aguilar-Salinas CA
Lipids Health Dis 2021 Jul 13;20(1):70. doi: 10.1186/s12944-021-01498-6. PMID: 34256778Free PMC Article
Pavanello C, Calabresi L
Curr Opin Lipidol 2020 Aug;31(4):232-237. doi: 10.1097/MOL.0000000000000697. PMID: 32618730
Saeedi R, Li M, Frohlich J
Clin Biochem 2015 May;48(7-8):472-5. Epub 2014 Aug 27 doi: 10.1016/j.clinbiochem.2014.08.014. PMID: 25172171
Gjone E
Ophthalmic Paediatr Genet 1988 Nov;9(3):167-9. doi: 10.3109/13816818809031494. PMID: 3068599
Narayanan S
CRC Crit Rev Clin Lab Sci 1979 Aug;11(1):31-51. doi: 10.3109/10408367909105853. PMID: 389551

Therapy

Bonilha I, Luchiari B, Nadruz W, Sposito AC
Arch Endocrinol Metab 2023 Jan 18;67(1):3-18. doi: 10.20945/2359-3997000000585. PMID: 36651718Free PMC Article
Amar MJA, Freeman LA, Nishida T, Sampson ML, Pryor M, Vaisman BL, Neufeld EB, Karathanasis SK, Remaley AT
Pharmacol Res Perspect 2020 Feb;8(1):e00554. Epub 2019 Dec 29 doi: 10.1002/prp2.554. PMID: 31893124Free PMC Article
Shamburek RD, Bakker-Arkema R, Auerbach BJ, Krause BR, Homan R, Amar MJ, Freeman LA, Remaley AT
J Clin Lipidol 2016 Mar-Apr;10(2):356-67. Epub 2015 Dec 23 doi: 10.1016/j.jacl.2015.12.007. PMID: 27055967Free PMC Article
Rousset X, Shamburek R, Vaisman B, Amar M, Remaley AT
Curr Atheroscler Rep 2011 Jun;13(3):249-56. doi: 10.1007/s11883-011-0171-6. PMID: 21331766Free PMC Article
Marzal-Casacuberta A, Blanco-Vaca F, Ishida BY, Julve-Gil J, Shen J, Calvet-Márquez S, González-Sastre F, Chan L
J Biol Chem 1996 Mar 22;271(12):6720-8. doi: 10.1074/jbc.271.12.6720. PMID: 8636092

Prognosis

Strazzella A, Ossoli A, Calabresi L
Cells 2021 Mar 31;10(4) doi: 10.3390/cells10040764. PMID: 33807271Free PMC Article
Pavanello C, Calabresi L
Curr Opin Lipidol 2020 Aug;31(4):232-237. doi: 10.1097/MOL.0000000000000697. PMID: 32618730
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
Hirashio S, Ueno T, Naito T, Masaki T
Clin Exp Nephrol 2014 Apr;18(2):189-93. Epub 2013 Oct 31 doi: 10.1007/s10157-013-0895-4. PMID: 24174160
Rousset X, Vaisman B, Amar M, Sethi AA, Remaley AT
Curr Opin Endocrinol Diabetes Obes 2009 Apr;16(2):163-71. doi: 10.1097/med.0b013e328329233b. PMID: 19306528Free PMC Article

Clinical prediction guides

Vitali C, Bajaj A, Nguyen C, Schnall J, Chen J, Stylianou K, Rader DJ, Cuchel M
J Lipid Res 2022 Mar;63(3):100169. Epub 2022 Jan 20 doi: 10.1016/j.jlr.2022.100169. PMID: 35065092Free PMC Article
Strazzella A, Ossoli A, Calabresi L
Cells 2021 Mar 31;10(4) doi: 10.3390/cells10040764. PMID: 33807271Free PMC Article
Pavanello C, Calabresi L
Curr Opin Lipidol 2020 Aug;31(4):232-237. doi: 10.1097/MOL.0000000000000697. PMID: 32618730
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
Rousset X, Vaisman B, Amar M, Sethi AA, Remaley AT
Curr Opin Endocrinol Diabetes Obes 2009 Apr;16(2):163-71. doi: 10.1097/med.0b013e328329233b. PMID: 19306528Free PMC Article

Recent systematic reviews

Vitali C, Bajaj A, Nguyen C, Schnall J, Chen J, Stylianou K, Rader DJ, Cuchel M
J Lipid Res 2022 Mar;63(3):100169. Epub 2022 Jan 20 doi: 10.1016/j.jlr.2022.100169. PMID: 35065092Free PMC Article
Mehta R, Elías-López D, Martagón AJ, Pérez-Méndez OA, Sánchez MLO, Segura Y, Tusié MT, Aguilar-Salinas CA
Lipids Health Dis 2021 Jul 13;20(1):70. doi: 10.1186/s12944-021-01498-6. PMID: 34256778Free PMC Article

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