Lysosomal acid lipase deficiency (LAL-D) is a rare, chronic, progressive inherited disorder. It affects the body’s ability to produce an enzyme called lysosomal acid lipase (LAL). This enzyme is needed for the breakdown of fats (lipids) and cholesterol in your cells. When the LAL enzyme is missing or deficient, fats accumulate in organs and tissues throughout the body, primarily leading to liver disease and high “bad cholesterol,” which is linked to cardiovascular disease.
LAL-D is an autosomal recessive inherited disorder, meaning that both parents must pass on a defective gene to the affected child. The disorder is usually passed on by two parents that are carriers – meaning their health is not affected – but both parents have one abnormal gene (recessive gene) and one normal gene (dominant gene) for the condition. When both parents are carriers, there is a 25% chance of having an affected child with each pregnancy.
LAL-D is caused by abnormalities in the LIPA gene, which is responsible for the production of the enzyme LAL. Abnormalities in this gene result in little to no LAL enzyme activity.
The LAL enzyme plays a major role in breaking down certain lipids and cholesterol, including low density lipoproteins (LDL), the type of cholesterol referred to as “bad cholesterol.” When there is a decrease or loss of the LAL enzyme, lipids and cholesterol do not get processed; they build up in cells and organs throughout the body, including the spleen, liver, and blood vessel walls.
High levels of LDL, or bad cholesterol, are associated with cardiovascular complications, such as heart attack and stroke. Lipid accumulation in the liver can lead to fibrosis (first stage of liver scarring), cirrhosis (more advanced stage of scarring), and eventually liver failure.
LAL-D can affect many systems throughout the body. Potential complications of LAL-D include damage to the:
LAL-D is an ultra-rare disease, which is defined as a disease that affects fewer than
20 people per one million of the general population. It can affect individuals of any gender or ethnic background, with the incidence being higher for people of Persian-Jewish descent.
The disease affects individuals of all ages from infancy through adulthood; however, manifestations of the disease vary across the lifespan. Infants with LAL-D begin to show severe symptoms about one month of age that rapidly progress to life-threatening complications, with death typically occurring before six months of age. Historically, LAL-D in infants was called Wolman disease.
In children and adults, symptoms may appear early or the disease may go unrecognized because the individual feels well and has no symptoms. If initial signs and symptoms are mild, patients and healthcare providers may not suspect a progressive disease and the person may not be diagnosed until later in life. Historically, late onset LAL-D was known as cholesteryl ester storage disease (CESD). However, researchers now recognize that CESD and Wolman disease are simply different presentations along a continuum of just one disease – LAL-D.
Infants, children, and adults who suffer from LAL-D experience a wide range of symptoms.
Some of the more common signs and symptoms of LAL-D in infants include:
Children and adults may not experience symptoms. An enlarged liver may be detected on a routine physical exam. Adolescents may have an abnormal lipid profile on routine screening. The first sign in adults may be elevated liver enzymes seen on a blood test. As liver damage progresses, signs and symptoms may include:
A diagnosis of LAL-D may sometimes be delayed by months or even years since many of the signs and symptoms associated with the disorder are similar to those of other more common conditions, like nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Additionally, patients can look and feel healthy until the condition is advanced.
LAL-D is diagnosed by a blood test that measures the activity of the LAL enzyme. Other supportive tests that your healthcare provider may order include genetic testing and a liver biopsy. Biopsy results can help access liver damage, but cannot be used to diagnose LAL-D, since similar liver damage can occur from other diseases.
In December 2015, the U.S. Food and Drug Administration (FDA) approved Kanuma (sebelipase alfa), the first therapy that treats the underlying cause of the disease. Previously, there were only supportive therapies available for LAL-D.
Supportive treatments used to manage LAL-D include the following, however, they have limitations:
Statins and other lipid-lowering agents
Stem cell transplant
Kanuma works differently from supportive therapies; it addresses the underlying cause of the disease by replacing the LAL enzyme that is deficient. This is referred to as enzyme replacement therapy. Kanuma is approved to treat LAL-D patients of all ages. It is given intravenously (IV) once a week for infants presenting within the first six months of life, and once every other week for children and adults; it needs to be given indefinitely.
Kanuma has been shown to:
The most commonly reported side effects of Kanuma in infants include diarrhea, vomiting, fever, runny nose, cough, and hives. The most commonly reported side effects in children and adults include headache, fever, inflammation of the throat and nasal passages, constipation, and nausea.
Allergic reactions, sometimes severe, have been reported in patients treated with Kanuma. Therefore, the drug must be administered in an appropriate medical setting by a healthcare professional.
Additional resources for information and support regarding LAL-D include:
As a patient living with a rare liver disease, you have several rights that can empower you throughout your health journey. Although every patient’s diagnosis and treatment plan are different, these rights can help you develop better working relationships with the members of your health care team and determine the best path forward for you. View ALF’s Patient Bill of Rights and information from ALF’s 2022 Rare Liver Disease Summit.
Clinical trials are research studies that test how well new medical approaches work in people. Before an experimental treatment can be tested on human subjects in a clinical trial, it must have shown benefit in laboratory testing or animal research studies. The most promising treatments are then moved into clinical trials, with the goal of identifying new ways to safely and effectively prevent, screen for, diagnose, or treat a disease.
Speak with your doctor about the ongoing progress and results of these trials to get the most up-to-date information on new treatments. Participating in a clinical trial is a great way to contribute to curing, preventing and treating liver disease and its complications.
Start your search here to find clinical trials that need people like you.
Last updated on August 16th, 2023 at 03:28 pm