Lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) or Wolman disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breaking down fatty material (cholesteryl esters and triglycerides) in the body. Infants, children, and adults who have LAL deficiency experience a range of serious health problems. The lack of the LAL enzyme can lead to a build-up of fatty material in several body organs, including the liver, spleen, gut, the wall of blood vessels, and other important organs.

The classic presentation is vomiting and failure to thrive or failure to gain weight in a newborn, with chalky bilateral adrenal calcifications on imaging, with life expectancy rarely exceeding a year. Very low levels of the LAL enzyme lead to LAL deficiency. LAL deficiency typically affects infants in the first year of life. The accumulation of fat in the walls of the gut in early-onset disease leads to serious digestive problems, including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age (failure to thrive). As the disease progresses, it can cause life-threatening liver dysfunction or liver failure.

Infants are chronically ill from birth, and rarely survive beyond the first year of life. In 2015, an enzyme replacement therapy, sebelipase alfa, was approved in the US and EU. The therapy was additionally approved in Japan in 2016.