Lecithin cholesterol acyltransferase deficiency
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2] Synonyms and keywords: LCAT deficiency, dyslipoproteinemic corneal dystrophy, fish eye disease, Norum disease, partial LCAT deficiency
Overview
Historical Perspective
- In 1962, Glomset identified an enzyme (plasma fatty acid transferase) which transfers fatty acid onto free cholesterol to make a cholesterol ester. This helps in the formation of a mature HDL particle a crucial step in reverse cholesterol transport [1].
- In 1967, Norum and Gjone described a disease for the first time in a patient from Norway with features of normochromic anemia, protienuria and corneal lipid deposits[2].
- In 1967, Norum and Gjone reported that two sisters of the affected patient had similar presentation along with low levels of cholesterol esters and lysolecithin in the serum, with increased total body cholesterol, triglyceride and phospholipid. Foam cells in the bone marrow and glomerulus were demonstrated on microscopy. Patients had absent hepatomegaly and normal tonsils differentiating it from liver disease causing the defect in esterification and Tangier disease. Low serum cholesterol esters were attributed to the LCAT enzyme deficiency[3].
- In 1986, McLean and colleagues reported the complete gene sequence and sites expression of Lecithin cholesterol acyl transferase gene(LCAT). The location of the gene is identified to be on q21-22 region of chromosome 16 [4] and is synthesized mainly in the liver.
Demographics, Natural History and Complications
Pathophysiology
Pathogenesis
| LCAT cleaves fatty acid from phosphotidylcholine | |||||||||||||||||||
| Transfers fatty acid to beta hydroxyl group of free cholesterol | |||||||||||||||||||
| Forms Cholesterol ester(CE) and lysophosphotidylcholine | |||||||||||||||||||
- LCAT helps in reverse cholesterol transport by:[5]
**Cholesterol esters due to the hydrophobic nature occupy the core of the lipoprotien, which prevent the backflow of cholesterol into the cells.
- LCAT promotes the efflux of free cholesterol from the cells via ABCA1 by creating a concentration gradient.
- Majority of the enzyme is associated with HDL C, very small amount with LDL C, and nothing with VLDL.[6]
Genetics
- Autosomal Recessive
- Obligate Heterozygous patients have normal LCAT levels.
Microscopy
Classification
Diagnosis
History and Symptoms
Laboratory Findings
Others
Treatment
Medical Therapy
Surgical Therapy
References
- ↑ GLOMSET JA (1962). "The mechanism of the plasma cholesterol esterification reaction: plasma fatty acid transferase". Biochim Biophys Acta. 65: 128–35. PMID 13948499.
- ↑ Norum KR, Gjone E (1967). "Familial serum-cholesterol esterification failure. A new inborn error of metabolism". Biochim Biophys Acta. 144 (3): 698–700. PMID 6078131.
- ↑ Gjone E, Norum KR (1968). "Familial serum cholesterol ester deficiency. Clinical study of a patient with a new syndrome". Acta Med Scand. 183 (1–2): 107–12. PMID 5669813.
- ↑ McLean J, Wion K, Drayna D, Fielding C, Lawn R (1986). "Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression". Nucleic Acids Res. 14 (23): 9397–406. PMC 311966. PMID 3797244.
- ↑ Tall AR (1990). "Plasma high density lipoproteins. Metabolism and relationship to atherogenesis". J Clin Invest. 86 (2): 379–84. doi:10.1172/JCI114722. PMC 296738. PMID 2200802.
- ↑ Chen CH, Albers JJ (1982). "Distribution of lecithin-cholesterol acyltransferase (LCAT) in human plasma lipoprotein fractions. Evidence for the association of active LCAT with low density lipoproteins". Biochem Biophys Res Commun. 107 (3): 1091–6. PMID 7138515.