Familial LCAT deficiency

Other Names: FLD Norum disease Complete LCAT deficiency familial lecithin-cholesterol acyltransferase deficiency FLD LCAT deficiency lecithin acyltransferase deficiency lecithin:cholesterol acyltransferase deficiency

Familial LCAT deficiency is a genetic disorder that affects the body's ability to process (metabolize) cholesterol. It is characterized by cloudiness of the clear front surface of the eye (corneal opacities), a shortage of red blood cells (hemolytic anemia), and kidney failure. Familial LCAT deficiency is one of two types of LCAT deficiency; the other type of LCAT deficiency is fish-eye disease.

Epidemiology

Familial LCAT deficiency is a rare disorder. Approximately 70 cases have been reported in the medical literature.

Cause

Familial LCAT deficiency is caused by mutations in the LCAT gene. This gene provides instructions for making an enzyme called lecithin-cholesterol acyltransferase (LCAT).

The LCAT enzyme plays a role in removing cholesterol from the blood and tissues by helping it attach to molecules called lipoproteins, which carry it to the liver. Once in the liver, the cholesterol is redistributed to other tissues or removed from the body. The enzyme has two major functions, called alpha- and beta-LCAT activity. Alpha-LCAT activity helps attach cholesterol to a lipoprotein called high-density lipoprotein (HDL). Beta-LCAT activity helps attach cholesterol to other lipoproteins called very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL).

LCAT gene mutations that cause complete LCAT deficiency either prevent the production of LCAT or impair both alpha-LCAT and beta-LCAT activity, reducing the enzyme's ability to attach cholesterol to lipoproteins. Impairment of this mechanism for reducing cholesterol in the body leads to cholesterol deposits in the corneas, kidneys, and other tissues and organs. LCAT gene mutations that affect only alpha-LCAT activity cause a related disorder called fish-eye disease that affects only the corneas.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms

The signs and symptoms of familial LCAT deficiency are thought to be caused by a buildup of cholesterol in different areas of the body. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals.

The earliest symptom of familial LCAT deficiency, typically occurring in childhood, is cloudiness in the front surface of the eye (cornea), known as corneal opacities.

Kidney disease, sometimes leading to kidney failure, usually begins in adolescence or early adulthood. Other symptoms often found in individuals with LCAT deficiency include:

• Hemolytic anemia (shortage of red blood cells)
• Enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy)
• Accumulation of fatty deposits in the artery walls (atherosclerosis)
• Swelling of the optic nerve (papilledema)
• A buildup of fat under the surface of the skin (xanthelasma)
• Symptoms of kidney failure, such as high blood pressure

Diagnosis

CBC: normochromic normocytic anemia Urinalysis: proteinuria in young adults (suggestive of kidney failure) Blood Chemistries: elevated blood urea nitrogen (BUN) and creatinine (suggestive of kidney failure) Lipid Panel: low high-density lipoprotein (HDL) < 10 mg/dL, elevated very low-density lipoprotein (VLDL) and triglycerides, high plasma unesterified cholesterol, and low plasma cholesterol ester Plasma LCAT activity: decreased (determined by decreased ability to esterify radioactive cholesterol in exogenous lipoproteins)

Treatment

Although there is no cure for familial LCAT deficiency, there are ways to manage the signs and symptoms including:

• Dialysis and kidney transplant as needed for individuals who develop kidney failure
• Corneal transplantation for individuals with corneal opacities and severely reduced vision
• Dietary restriction of fat intake
• Exercise
• Medications to lower cholesterol (statins)
• Blood pressure medications (angiotensin receptor blockers)

Prognosis

The long-term outlook (prognosis) for people with familial LCAT deficiency varies depending on the severity of associated signs and symptoms. The most serious complication of familial LCAT deficiency is kidney failure.

NIH genetic and rare disease info

• NIH info on Familial LCAT deficiency

Familial LCAT deficiency is a rare disease.

Familial LCAT deficiency Resources
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