lysosomal acid lipase deficiency

What is Lysosomal Acid Lipase Deficiency?

Lysosomal acid lipase (LAL) deficiency is an inherited condition caused by harmful genetic changes (mutations) in the LIPA gene. Mutations in LIPA lead to a decrease or complete loss of acid lipase activity. Without acid lipase, the body cannot properly break down fatty substances (lipids), including cholesteryl esters (a form of cholesterol) and triglycerides (a type of fat). These lipids instead build up and damage organs such as the spleen, the liver, bone marrow, the small intestine, the gland located above the kidneys (the adrenal gland), and lymph nodes. There are two types of LAL deficiency, which are Wolman disease and cholesterol ester storage disease (CESD).

Wolman Disease

Individuals with Wolman disease typically have little to no acid lipase activity and often develop symptoms within the first few weeks of life. Symptoms include liver failure and enlargement of organs such as the liver and spleen (enlargement of the liver is called hepatomegaly, and enlargement of the spleen is called esplenomegaly). Gastrointestinal issues such as diarrhea, vomiting, swelling of the abdomen (abdominal distension) and increased fat content in the stool (steatorrhea) are common. Individuals also have severe malnutrition and poor growth (failure to thrive). Enlargement and calcification of the adrenal glands can cause a life-threatening absence of important hormones in the body (adrenal insufficiency).

Cholesterol Ester Storage Disease

Cholesterol Ester Storage Disease (CESD) is a milder disorder that progresses more slowly than Wolman disease. Individuals with CESD tend to have more remaining acid lipase activity. The age of symptom onset ranges from early childhood to adulthood. Symptoms include hepatomegaly, liver disease, gastrointestinal issues, and poor growth. Individuals have abnormal lipid levels in their blood (dyslipidemia). This can result in the early-onset formation of plaques in the arteries (coronary artery disease), which may cause complications such as heart attack or stroke.

How common is Lysosomal Acid Lipase Deficiency?

The incidence of LAL deficiency is unknown, though it has been estimated to occur in 1 in 40,000 to 1 in 300,000 individuals. It may be more frequent among certain ethnic groups, such as individuals of European, Hispanic, or Iranian Jewish descent.

How is Lysosomal Acid Lipase Deficiency treated?

Enzyme replacement therapy (ERT), which provides the acid lipase enzyme to affected individuals through an IV, has recently become available to treat both subtypes of LAL deficiency. Studies suggest that ERT increases survival in individuals with Wolman disease and reduces some of the symptoms associated with both Wolman disease and CESD. Additional research is needed to fully understand the long-term benefits and limitations of ERT for the treatment of LAL deficiency.

Procedures such as bone marrow transplant and liver transplant have been used to treat LAL. Successful bone marrow transplant has cured several cases of Wolman disease.

Other treatments focus on addressing an individual's specific symptoms. For example, treatment with medications can be used to manage abnormal lipid levels or adrenal insufficiency. A nutrition team may provide dietary recommendations to help with malnutrition and growth.

What is the prognosis for an individual with Lysosomal Acid Lipase Deficiency?

Infants with Wolman disease typically die within the first year of life due to organ damage and malnutrition. However, treatment with enzyme replacement therapy increases life expectancy for this condition. Some individuals with CESD may have a normal life span. In other cases, complications from coronary artery disease and liver disease may lead to early death. Available treatments can prolong life expectancy in many individuals with CESD.