Lecithin cholesterol acyltransferase deficiency
| Lecithin cholesterol acyltransferase deficiency | |
|---|---|
| Classification and external resources | |
| Specialty | endocrinology |
| ICD-10 | E78.6 |
| ICD-9-CM | 272.5 |
| OMIM | 245900 136120 |
| DiseasesDB | 7343 |
| eMedicine | med/1270 |
| MeSH | D007863 |
Lecithin cholesterol acyltransferase deficiency (LCAT deficiency) is disorder of lipoprotein metabolism.[1]
Lecithin cholesterol acyltransferase catalyzes the formation of cholesterol esters in lipoproteins.
Types
- familial LCAT deficiency in which there is complete LCAT deficiency.
- fish eye disease in which there is a partial deficiency.
Both are autosomal recessive disorders caused by mutations of the LCAT gene located on chromosome 16q22.
Presentation
A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free cholesterol on HDL to cholesterol ester and allows the maturation of HDL. LCAT deficiency does not allow for HDL maturation resulting in its rapid catabolism of circulating apoA-1 and apoA-2. The remaining form of HDL resembles nascent HDL. Symptoms of the familial form include diffuse corneal opacities, target cell hemolytic anemia and proteinuria with renal failure. Fish eye disease only causes progressive corneal opacification.
Mortality and morbidity
Renal failure is the major cause of morbidity and mortality in complete LCAT deficiency, while in partial deficiency (fish eye disease) major cause for morbidity is visual impairment due to corneal opacity. These patients have low HDL cholesterol but surprisingly premature atherosclerosis is not seen. However, there are some reported cases.
Signs and symptoms
In complete LCAT deficiency patients may present with Anemia, Corneal opacities, Hepatosplenomegaly, renal insufficiency while in partial deficiency (fish eye disease) corneal opacities is the main finding with hepatosplenomegaly.
Diagnosis
Battery of tests are required such as CBC for anemia, kidney functions, urine for proteinuria, Lipid profile, these patients have very low HDL cholesterol and high triglyceride level, High free cholesterol and low cholesterol esters levels. However definitive diagnosis rests with LCAT gene analysis for mutation and functional activity.
References
- ↑ Kuivenhoven JA, Pritchard H, Hill J, Frohlich J, Assmann G, Kastelein J (February 1997). "The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes". J. Lipid Res. 38 (2): 191–205. PMID 9162740.
- ↑ Calabresi L, Pisciotta L, Costantin A, Frigerio I, Eberini I, Alessandrini P, Arca M, Bon GB, Boscutti G, Busnach G, Frasc G, Gesualdo L, Gigante M, Lupattelli G, Montali A, Pizzolitto S, Rabbone I, Rolleri M, Ruotolo G, Sampietro T, Sessa A, Vaudo G, Cantafora A, Veglia F, Calandra S, Bertolini S, Franceschini G (Sep 2005). "The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families.". Arteriosclerosis, thrombosis, and vascular biology. 25 (9): 1972–1978. doi:10.1161/01.ATV.0000175751.30616.13. ISSN 1079-5642. PMID 15994445.