lysosomal acid lipase deficiency
What is Lysosomal Acid Lipase Deficiency?
Lysosomal acid lipase (LAL) deficiency is an inherited disease characterized by an absence or deficiency of acid lipase, an enzyme that is necessary for the body to properly metabolize lipids (fatty substances). The effects of LAL deficiency are directly correlated to the body's ability to break down cholesteryl esters (a form of cholesterol) and triglycerides (a type of fat). The end result is an accumulation of lipids in the organs, mainly the spleen, liver, bone marrow, small intestine, adrenal glands, and lymph nodes, which is damaging. LAL deficiency likely represents a spectrum of disease, but sub-categories of the disease have been described, including Wolman disease and cholesteryl ester storage disease (CESD).
Individuals with Wolman disease typically have little to no acid lipase activity and tend to develop symptoms within the first few weeks of life. Symptoms include an enlarged liver and spleen (hepatosplenomegaly), an enlargement of the abdomen, vomiting, diarrhea, excess fat in the feces, a deficiency of red blood cells, yellowing of the skin or eyes, calcium deposits in the adrenal glands, and a failure to maintain a healthy weight for age.
Cholesteryl Ester Storage Disease (CESD)
Individuals with CESD, who tend to have higher levels of acid lipase activity, may develop symptoms from the first year of life to adulthood. Symptoms are usually milder than those of Wolman disease and the disease generally progresses more slowly. Most individuals present with liver enlargement that indicates varying degrees of organ damage (such as an accumulation of fat in liver cells or liver cirrhosis). Enlargement of the spleen is also possible and affected individuals frequently develop high cholesterol, elevated triglycerides, and reduced levels of HDL ("good cholesterol"), which results in the formation of plaques in the arteries (coronary artery disease).
How common is Lysosomal Acid Lipase Deficiency?
It is currently unknown how often LAL deficiency occurs in the general population. Recent data suggest that the frequency of the condition may have previously been underestimated, primarily because of a lack of disease recognition and the wide disease spectrum. In addition, the frequency of the condition varies depending on the population studied. Wolman disease has been estimated to occur in 1 in 4,200 individuals in the Iranian Jewish population alone, and in 1 in 8,100 individuals in the Iranian and Uzbekistani/Bukharan populations together. CESD is estimated to be most common in the Caucasian and Hispanic populations, occurring in at least 1 in 225,000 to 1 in 350,000 individuals. Overall, it is thought that Wolman disease is less common than CESD.
How is Lysosomal Acid Lipase Deficiency treated?
Bone marrow transplantation has been shown to successfully cure Wolman disease, but there is a high mortality rate associated with the procedure. When bone marrow transplantation is not performed, the condition is considered fatal and treatment is palliative. The treatment of CESD generally focuses on the patient's symptoms. Affected individuals are typically monitored by laboratory examinations, imaging studies, and evaluation of heart function. Medications (such as statins) may be used to treat high cholesterol and high triglycerides, and liver transplantation may become necessary.
Enzyme replacement therapy is available for both subtypes of LAL deficiency and studies have shown that it may prolong survival.
What is the prognosis for a person with Lysosomal Acid Lipase Deficiency?
Because of the damage to organs and the malnutrition that results from the inability to metabolize fatty acids, infants with Wolman disease typically die within the first year of life, without a successful bone marrow transplant or enzyme replacement therapy. Lifespan for individuals with CESD is expected to be longer than individuals with Wolman disease, and available treatments may prolong life into adulthood. However, approximately 50% of individuals with CESD die in the second decade of life due to complications of liver disease or heart disease.