Lysosomal Acid Lipase Deficiency (CESD)

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MedlinePlus Genetics: ⁴² Lysosomal acid lipase deficiency is an inherited condition characterized by problems with the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of fats (lipids) accumulate in cells and tissues throughout the body, which typically causes liver disease. There are two forms of the condition. The most severe and rarest form begins in infancy. The less severe form can begin from childhood to late adulthood.In the severe, early-onset form of lysosomal acid lipase deficiency, lipids accumulate throughout the body, particularly in the liver, within the first weeks of life. This accumulation of lipids leads to several health problems, including an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption). In addition, affected infants often have calcium deposits in small hormone-producing glands on top of each kidney (adrenal glands), low amounts of iron in the blood (anemia), and developmental delay. Scar tissue quickly builds up in the liver, leading to liver disease (cirrhosis). Infants with this form of lysosomal acid lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year.In the later-onset form of lysosomal acid lipase deficiency, signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late adulthood. Nearly all affected individuals develop an enlarged liver (hepatomegaly); an enlarged spleen (splenomegaly) may also occur. About two-thirds of individuals have liver fibrosis, eventually leading to cirrhosis. Approximately one-third of individuals with the later-onset form have malabsorption, diarrhea, vomiting, and steatorrhea. Individuals with this form of lysosomal acid lipase deficiency may have increased liver enzymes and high cholesterol levels, which can be detected with blood tests.Some people with this later-onset form of lysosomal acid lipase deficiency develop an accumulation of fatty deposits on the artery walls (atherosclerosis). Although these deposits are common in the general population, they usually begin at an earlier age in people with lysosomal acid lipase deficiency. The deposits narrow the arteries, increasing the chance of heart attack or stroke. The expected lifespan of individuals with later-onset lysosomal acid lipase deficiency depends on the severity of the associated health problems.The two forms of lysosomal acid lipase deficiency were once thought to be separate disorders. The early-onset form was known as Wolman disease, and the later-onset form was known as cholesteryl ester storage disease. Although these two disorders have the same genetic cause and are now considered to be forms of a single condition, these names are still sometimes used to distinguish between the forms of lysosomal acid lipase deficiency.

MalaCards based summary: Lysosomal Acid Lipase Deficiency, also known as wolman disease, is related to cholesterol ester storage disease and hypercholesterolemia, familial, 1, and has symptoms including vomiting and diarrhea. An important gene associated with Lysosomal Acid Lipase Deficiency is LIPA (Lipase A, Lysosomal Acid Type), and among its related pathways/superpathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Plasma lipoprotein assembly, remodeling, and clearance. The drugs Prednisolone phosphate and Prednisolone acetate have been mentioned in the context of this disorder. Affiliated tissues include liver, spleen and bone marrow, and related phenotypes are nausea and vomiting and global developmental delay

NINDS: ⁵² Acid lipase disease or deficiency occurs when the enzyme needed to break down certain fats that are normally digested by the body is lacking or missing, resulting in the toxic buildup of these fats in the body’s cells and tissues. These fatty substances, called lipids, include fatty acids, oils, and cholesterol. Two rare lipid storage diseases are caused by the deficiency of the enzyme lysosomal acid lipase, both of which are interited and affect males and females Wolman’s disease (also known as acid lipase deficiency) is marked by the buildup of cholesteryl esters (normally a tranport form of cholesterol that brings nutrients into the cells and carries out waste) and triglycerides (a chemical form in which fats exist in the body). Infants with the disorder appear normal at birth but quickly develop progressive mental deterioration, low muscle tone, enlarged liver and grossly enlarged spleen, gastrointestinal problems, jaundice, anemia, vomiting, and calcium deposits in the adrenal glands, which causes them to harden. Cholesteryl ester storage disease (CESD) is an extremely rare disorder that results from storage of cholesteryl esters and triglycerides in cells in the blood and lymph and lymphoid tissue. Children develop an enlarged liver, leading to cirrhosis and chronic liver failure before adulthood. Children may also develop calcium deposits in the adrenal glands and jaundice. Onset varies, and the disorder may not be diagnosed until adulthood.

Orphanet ⁵⁸ Lysosomal acid lipase deficiency: A rare, progressive metabolic liver disease due to marked to complete lysosomal acid lipase deficiency and characterized by dyslipidemia and massive lipid accumulation leading to hepatomegaly and liver dysfunction, splenomegaly, accelerated atherosclerosis.

Wolman disease: A severe form of lysosomal acid lipase deficiency characterized by rapidly progressive lipid accumulation in organs and tissues that presents in the neonatal or infantile period with massive hepatosplenomegaly, liver failure, diarrhea/steatorrhea and vomiting.

Cholesteryl ester storage disease: A form of lysosomal acid lipase deficiency characterized by progressive cholesterol esters and triglyceride accumulation in tissues and organs typically presenting with hepatosplenomegaly, liver dysfunction and/or dyslipidemia.

GARD: ¹⁹ Cholesteryl ester storage disease is is a type of lysosomal acid lipase deficiency. It is an inherited disease that causes a buildup of fats (lipids) in the tissues and organs of the body and calcium deposits in the adrenal glands. The liver is most severely affected in most cases. Some people with Cholesteryl ester storage disease may develop liver cirrhosis that progresses to liver failure. People with Cholesteryl ester storage disease may also build up fatty deposits on the artery walls (atherosclerosis). This buildup can narrow the arteries and increase the risk for heart attack or stroke. Cholesteryl ester storage disease is caused by genetic changes in the LIPA gene. It is inherited in an autosomal recessive manner.

OMIM®: ⁵⁷ Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease and cholesteryl ester storage disease (CESD). Wolman disease is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (summary by Du et al., 2001). (278000) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot ⁷³ Cholesteryl ester storage disease: A mild manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. It is characterized by late-onset.

Wolman disease: A severe manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. WD occurs in infancy and is nearly always fatal before the age of 1 year.

Wikipedia: ⁷⁵ Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) is an autosomal recessive inborn error of... more...

Clinical features from OMIM®:

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