Lysosomal acid lipase deficiency is a rare genetic condition that causes fat to build up in your body’s cells, especially in your liver and spleen.

Lysosomal acid lipase deficiency (LALD) is a rare genetic condition that causes problems with lipid (fat) metabolism. While it’s unclear exactly how rare the condition is, it may affect 1 in 40,000 to 1 in 300,000 people.

LALD causes fats to build up in cells in your body, particularly in your liver and spleen. This can lead to serious health complications, including liver disease and malnutrition.

There are two forms of LALD. The more severe type, called Wolman disease, begins in infancy. The second type, which is often more manageable, is called cholesteryl ester storage disease (CESD) and can develop during childhood, adolescence, or adulthood.

The signs and symptoms of the early onset form of LALD (Wolman disease) can include:

The signs and symptoms of the later onset form of LALD (CESD) can be more variable and may include:

LALD is caused by mutations in the LIPA gene, which tells your cells how to make the enzyme lysosomal acid lipase (LAL). LAL is found in the part of a cell called the lysosome, which breaks down and recycles substances the cell no longer needs.

LAL usually helps break down cholesteryl esters and triglycerides into cholesterol and fatty acids, which are then sent to your liver to be removed from your body.

But mutations in LIPA lead to decreased production of LAL in CESD and no production of LAL in Wolman disease. As a result:

  • Cholesteryl esters, triglycerides, and other fats build up within lysosomes.
  • Your body finds other ways to make cholesterol, which can lead to increases in blood cholesterol levels.
  • Excess fats are still sent to your liver, but they cannot be properly broken down and instead begin to build up, leading to liver disease.

LALD is inherited in an autosomal recessive manner. This means you’ll have LALD only if you receive two copies of the mutated LIPA gene — one from each parent.

LALD can be difficult to diagnose because its symptoms overlap with those of some more common conditions. Healthcare professionals often mistake it for conditions such as familial hypercholesterolemia and nonalcoholic fatty liver disease.

But some features can be unique to LALD:

  • Early onset: Doctors may suspect Wolman disease when the following signs and symptoms occur together:
    • enlarged liver
    • vomiting and diarrhea
    • failure to thrive
    • adrenal gland calcifications
  • Late onset: Observations that can suggest CESD include:
    • enlarged spleen in the absence of other causes, such as infections or blood cancers

Doctors may use the following tests to help diagnose LALD:

However, these tests alone cannot confirm a diagnosis of LALD. Additional tests are necessary.

Genetic testing can find mutations in the LIPA gene. Healthcare professionals can also perform tests to assess the level of LAL enzyme activity in a dried blood spot or in a sample of cells.

The Food and Drug Administration approved the medication sebelipase alfa (Kanuma) in 2015 to treat LALD. This medication can be used to treat both forms of the condition.

Kanuma is a type of enzyme replacement therapy. It replaces the LAL in your body so lipid metabolism can proceed as usual.

Kanuma is given intravenously once per week for early onset LALD and once every other week for later onset LALD. Lifelong treatment is usually necessary.

Before the approval of Kanuma, other treatments were predominantly used for LALD, including:

Your doctor will monitor the health of your liver, spleen, and cardiovascular system throughout your treatment.

Additionally, LALD often leads to nutritional deficiencies due to malabsorption, so nutritional monitoring is an important part of managing the condition.

There’s currently no cure for LALD. Continued treatment is necessary to reduce the effects of the condition. Regular monitoring of your overall health and nutrition is also essential.

There’s a big difference in the outlook between early onset and later onset LALD:

Early onset LALD (Wolman disease)

Wolman disease is more severe and progresses quickly. Death typically occurs within the first year of life. One small 2016 study found that the median age at death was 3.7 months.

However, the introduction of Kanuma has increased life expectancy with this condition. The results of two clinical trials estimated that 68% of infants treated with Kanuma would survive to age 5 years.

Later onset LALD (CESD)

CESD is associated with a variety of potential health complications, such as:

Generally, people with CESD can have a typical life expectancy, depending on their disease presentation.

Kanuma has also improved the outlook for people with CESD. A 2022 clinical trial found that those taking Kanuma had rapid improvement in markers of liver function and blood lipids. There was no progression of liver disease for up to 5 years.

LALD is a rare genetic condition that affects the metabolism of fats in your body. It leads to buildup of fats in cells, especially those in your liver and spleen.

There are two types of LALD. Early onset LALD begins in infancy, is more severe, and progresses quickly. Later onset LALD begins after infancy and is associated with complications such as liver disease and atherosclerosis.

LALD currently has no cure, and the outlook depends on the type of LALD a person has. Overall, treatment with enzyme replacement therapy has helped improve the outlook for LALD compared with earlier treatments.