Complete LCAT deficiency
Complete LCAT deficiency is a rare genetic disorder that primarily affects the eyes and kidneys, leading to corneal clouding, kidney disease, and hemolytic anemia.
Overview
Complete LCAT deficiency is a disorder that primarily affects the eyes and kidneys. In this condition, the clear front surface of the eyes (the corneas) gradually becomes cloudy, typically first appearing in early childhood as small grayish dots of cholesterol (opacities) distributed across the corneas. The cloudiness worsens over time and can lead to severely impaired vision.
Individuals often develop kidney disease beginning in adolescence or early adulthood, which can progress to kidney failure. Most also have hemolytic anemia, a premature breakdown of red blood cells that can cause pale skin, weakness, fatigue, and other complications.
Additional features reported in some individuals include enlargement of the liver (hepatomegaly), spleen (splenomegaly), lymph nodes (lymphadenopathy), or fatty deposits on artery walls.
Frequency: Complete LCAT deficiency is a rare disorder. Approximately 70 cases have been reported in the medical literature.
Symptoms
- Corneal clouding with grayish cholesterol opacities, beginning in early childhood and progressing to visual impairment.
- Kidney disease starting in adolescence or early adulthood, potentially leading to kidney failure.
- Hemolytic anemia (premature red blood cell breakdown), causing pale skin, weakness, and fatigue.
- Enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy) in some individuals.
- Accumulation of fatty deposits on arterial walls.
Causes & Risk Factors
Complete LCAT deficiency is caused by mutations in the LCAT gene, which provides instructions for making the enzyme lecithin‑cholesterol acyltransferase (LCAT). The LCAT enzyme helps remove cholesterol from blood and tissues by attaching it to lipoproteins that transport cholesterol to the liver for redistribution or excretion.
The enzyme has two major functions: alpha‑LCAT activity (attaches cholesterol to high‑density lipoprotein, HDL) and beta‑LCAT activity** (attaches cholesterol to very low‑density lipoprotein, VLDL, and low‑density lipoprotein, LDL). Mutations that cause complete LCAT deficiency either prevent production of LCAT or impair both alpha‑ and beta‑LCAT activities, reducing the enzyme’s ability to attach cholesterol to lipoproteins. This leads to cholesterol deposits in the corneas, kidneys, and other tissues.
Inheritance: The condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show signs or symptoms.
Diagnosis
The source material does not provide specific diagnostic criteria or testing methods for complete LCAT deficiency.
Treatment & Management
The source material does not detail treatment or management strategies for complete LCAT deficiency.
Other Names
- Familial LCAT deficiency
- Familial lecithin‑cholesterol acyltransferase deficiency
- FLD
- LCAT deficiency
- Lecithin acyltransferase deficiency
- Lecithin:cholesterol acyltransferase deficiency
- Norum disease
- Norum's disease
Genetic Information
- Gene: LCAT
Additional Resources
- Genetic Testing Registry: Norum disease
- Genetic and Rare Diseases Information Center: Familial LCAT deficiency
- National Organization for Rare Disorders (NORD)
- ClinicalTrials.gov
- OMIM: LECITHIN:CHOLESTEROL ACYLTRANSFERASE DEFICIENCY
- PubMed
References
- Calabresi L, et al. The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1972-8. doi:10.1161/01.ATV.0000175751.30616.13.
- Jahanzad I, Amoueian S, Attaranzadeh A. Familial lecithin‑cholesterol acyltransferase deficiency. Arch Iran Med. 2009 Mar;12(2):179-81.
- Roshan B, et al. Homozygous lecithin:cholesterol acyltransferase (LCAT) deficiency due to a new loss of function mutation and review of the literature. J Clin Lipidol. 2011 Nov-Dec;5(6):493-9. doi:10.1016/j.jacl.2011.07.002.
- Savel J, et al. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship--a review of LCAT deficiency. Vasc Health Risk Manag. 2012;8:357-61. doi:10.2147/VHRM.S29985.
- Shoji K, et al. Lecithin‑cholesterol acyltransferase (LCAT) deficiency without mutations in the coding sequence: a case report and literature review. Clin Nephrol. 2011 Oct;76(4):323-8. doi:10.5414/cn106484.