Also known as Late Onset Lysosomal Acid Lipase (LAL) Deficiency, CESD is an inherited disease that affects children (usually greater than 2 years old), adolescents and adults. In this disease, the body is missing an enzyme that breaks down fats (also known as lipids). As a result, these fats build up throughout the body mostly in the liver, spleen and blood vessels. This build up can cause an enlarged liver, leading to liver failure, as well as an increased risk for heart attack and stroke. The missing enzyme is known as lysosomal acid lipase (LAL). For the rest of this entry, we will refer to the condition as LAL Deficiency, specifically its Late Onset form.
Late Onset LAL Deficiency is a disease that gets worse over time. Some people develop symptoms during childhood, while others may not experience symptoms, or symptoms may not be recognized, until they are adults. The signs and symptoms can include:
- Abnormal blood test results (very low ‘good’ cholesterol, high ‘bad’ cholesterol and/or ‘high’ liver function tests)
- Enlarged liver (hepatomegaly), which may cause a constant nagging pain in the abdomen (belly area)
- Scarring of the liver known as cirrhosis, which can cause serious problems and lead to liver failure
- Enlarged spleen (splenomegaly), leading to abdominal pain and/or low blood cell counts (anemia, thrombocytopenia)
- A lipid build-up in the walls of major arteries and an increased risk of heart attacks and strokes.
Many of these signs and symptoms are also common in patients with other liver conditions such as Non Alcoholic Fatty Liver Disease (NAFLD) or Non Alcoholic Steatohepatitis (NASH).
LAL Deficiency is a genetic condition, which means is it caused by our genes. Genes are instructions that tell our bodies how to grow, develop and function. In every cell of our body, we have two copies of each gene. We inherit one copy from our mother and one copy from our father. Sometimes our genes do not work properly because there are changes in their codes, known as mutations. LAL Deficiency is caused by mutations in the LIPA gene. This gene tells our body how to make the LAL enzyme. The LAL enzyme breaks down fatty material into forms that our body can use. A person with the LAL Deficiency is missing some of the enzyme needed to break down fats.
LAL Deficiency is an autosomal recessive disease, which means it is inherited from your mother and your father.
See treatment below.
Patients with LAL Deficiency typically have high cholesterol and triglyceride levels in their blood (type II hyperlipidemia) and may have an injured liver because of the buildup of fats. The liver injuries may first be noticed as:
A big liver with high amounts of fat
Higher than normal liver function tests (AST or ALT)
Progressive and/or unexplained chronic liver disease
The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history (including family history) and special tests to check the activity level of the LAL enzyme. Confirming that there are mutations (genetic variations) in both copies of the LIPA gene is also a way to diagnose LAL Deficiency.
Testing information is available at the following websites:
Your physician may also contact the Biochemistry Laboratory at Yorkhill Children’s Hospital in Glasgow, Scotland for more information about Dried Blood Spot (DBS) enzyme activity testing via email: [email protected]
Enzyme replacement therapy
Researchers are currently studying enzyme replacement therapy for LAL Deficiency.
Enzyme replacement therapy (ERT) involves replacing a missing enzyme in individuals who are deficient or lack the particular enzyme in question.
Currently, there are no treatments that have been approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for LAL Deficiency. The high lipid levels in the blood are frequently treated with a combination of low-fat/ low-cholesterol diet and lipid-lowering medications such as statins, fibrates, cholestyramine and ezetimibe. Although these treatments can lower the lipid levels in the blood, there is no evidence that they improve the liver abnormalities.
A small number of people with Late Onset LAL Deficiency, who developed chronic liver disease, have been treated with a liver transplant.
Genetic counseling may be helpful for families with this disease.