Familial LCAT deficiency

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.^[1][3] Other symptoms often found in individuals with LCAT deficiency include:^[1][3]

• 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

Familial LCAT deficiency is a genetic disorder caused by mutations in the LCAT gene. The LCAT gene provides instructions for making an enzyme (protein) called lecithin-cholesterol acyltransferase (LCAT). This enzyme is involved in removing cholesterol from the blood and tissues by helping it attach to a group of proteins, called lipoproteins. The cholesterol is then transported to the liver and sent to other tissues in the body or removed from the body.

The LCAT enzyme has two major functions: alpha and beta LCAT activity. Alpha-LCAT activity helps attach cholesterol to a lipoprotein called high-density lipoprotein (HDL), while beta-LCAT activity helps attach cholesterol to other lipoproteins called low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).^[1][3]

In familial LCAT deficiency, LCAT gene mutations either prevent the production of the LCAT enzyme or impair both the alpha-LCAT and beta-LCAT activity, reducing the enzyme's ability to attach cholesterol to lipoproteins. This is known as a complete LCAT deficiency. This likely leads to a buildup (deposit) of cholesterol in tissues throughout the body, including the corneas and kidneys.^[1]

Familial LCAT deficiency is inherited in an autosomal recessive manner.^[4] This means that to have the deficiency, a person must have a mutation in both copies of the gene associated with the deficiency in each cell. People with familial LCAT deficiency inherit one mutated copy of the gene from each parent; each parent is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to have familial LCAT deficiency
• 50% chance to not have familial LCAT deficiency AND to only be a carrier like each parent
• 25% chance to not have familial LCAT deficiency AND not be a carrier

Although there is no cure for familial LCAT deficiency, there are ways to manage the signs and symptoms including:^[3][5]

• 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)

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.^[3][2]