Lysosomal acid lipase deficiency (LALD) is an inherited, progressive disease where the affected individuals have a problem with the enzyme that is essential for the breakdown of fats. As the result, these lipids can accumulate in various parts of the body affecting their normal function. This can cause conditions such as fatty liver disease and liver failure. LALD can affect individuals of all ages from infants to adults. Very low levels of LAL enzyme can result in the early onset LALD which is also known as Wolman disease. When it develops in infants, it can progress rapidly and cause life-threatening complications.
Causes
This develops as the result of the mutation in the gene LIPA which is essential for the production of an enzyme called lysosomal acid lipase. This enzyme is responsible for the breakdown of materials such as cholesteryl esters and triglycerides. The genetic mutation result in the deficiency of the functional enzyme and the severity of the condition is based on the quantity of enzyme deficiency. LALD causes the accumulation of materials such as lipid which accumulate in various tissues of the body that cannot be effectively removed from organs such as the liver resulting in liver disease. This condition is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The affected individual’s parents often are the carrier of a single copy of the genetic mutation and don’t necessarily exhibit any of the signs associated with this condition.
Symptoms
Individuals with this problem experience various health conditions that are caused by the accumulation of fatty materials in the organs such as the spleen, liver and the wall of the blood vessels. Most of the signs of this condition may not be evident which is identified with blood tests. However, some of the symptoms associated with LALD include failure to grow, jaundice, diarrhea, vomiting, enlarged abdomen and the problem with the normal absorption of food (malabsorption). In some cases, the symptoms may occur as the result of liver damage that includes jaundice, enlarged abdomen and easy bruising or bleeding.
Diagnosis
The proper diagnosis of LALD may be difficult as it presents symptoms similar to other conditions such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, among most of the cases, the affected individuals may continue to have a normal health and the problem may only become evident when it has advanced. The diagnosis is based on a blood test that checks the activity of LAL enzyme. A liver biopsy may also be important in determining the extent of liver damage although it cannot confirm the diagnosis. The molecular genetic testing can also help confirm the diagnosis by detecting the mutation responsible for causing this condition.
Treatment
The treatment consists of medications that help lower the level of cholesterol and to prevent the fat deposits in blood vessels. The enzyme replacement therapy with recombinant human LAL has proven to be beneficial although this is still under investigation.
References
http://www.liver.ca/liver-disease/types/Lysosomal_Acid_Lipase_Deficiency_(LALD).aspx
https://ghr.nlm.nih.gov/condition/lysosomal-acid-lipase-deficiency#inheritance
http://www.liverfoundation.org/abouttheliver/info/lald/#Q6
http://www.mpssociety.org.uk/diseases/related-diseases/lysosomal-acid-lipase-deficiency/
