Feature Blog Article
Feature Blog Article
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.
- Lysosomal Acid Lipase Deficiency is a rare, genetic condition that causes individuals to have an uncontrolled buildup of fatty material in their cells.
- Most people will have symptoms of Lysosomal Acid Lypase Deficiency by the age of 5.
How is LAL-D inherited?
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.
How does LAL-D affect the body?
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.
What are the complications of LAL-D?
LAL-D can affect many systems throughout the body. Potential complications of LAL-D include damage to the:
- Liver: Enlarged liver, fibrosis, cirrhosis, liver failure
- Cardiovascular System: Low amounts of good cholesterol, high amounts of bad cholesterol, heart attack and stroke
- Spleen: Enlarged spleen, low platelet count leading to bleeding problems
- Gastrointestinal System: Pain, bleeding, diarrhea, poor absorption of nutrients leading to malnutrition and poor growth
Who gets LAL-D?
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.
What are the signs and symptoms of 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:
- Failure to grow
- Enlarged abdomen
- Persistent vomiting and diarrhea
- Jaundice (yellowing of the skin and whites of the eyes)
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:
- Easy bruising or bleeding
- Ascites (enlarged abdomen due to accumulation of fluid)
- Jaundice (yellowing of the skin and whites of the eyes)
- Liver fibrosis or cirrhosis
- Premature cardiovascular events, for example, heart attack and stroke
How is LAL-D diagnosed?
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.
How is LAL-D treated?
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:
- Usually not sufficient when used alone to control high cholesterol
Statins and other lipid-lowering agents
- Lipid profile may improve, but it rarely returns to normal
Stem cell transplant
- Risks associated with the procedure
- Infants who receive a transplant still have a high death rate due to rapid disease progression
- Risks associated with procedure
- Transplant does not cure the disease
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:
- Reduce liver fat content
- Reduce liver enzymes
- Reduce the size of the spleen
- Improve lipid profiles by lowering levels of bad cholesterol and raising levels of good cholesterol
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.
What resources are available?
Additional resources for information and support regarding LAL-D include:
- National Organization for Rare Disorders (NORD): Provides rare disease information, resources, and financial assistance. Call 1-800-999-6673 or visit www.rarediseases.org
- LAL Solace: An online patient community for people with LAL-D. Visit www.lalsolace.org
- OneSource: Patient support and financial assistance information from Alexion Pharmaceuticals for patients prescribed Kanuma. Call 1-888-765-4747 or visit www.kanuma.com
- What are some symptoms I should expect?
- Have you treated other patients with this disease?
- What treatment options do I have?
- Are there changes in my diet to help with the issues of fat?
- Are there other lifestyle changes I should be making to promote liver wellness>?
- Can this disease develop into liver cancer?
- What is the survival rate?
There are many different types of liver disease. But no matter what type you have, the damage to your liver is likely to progress in a similar way.
Whether your liver is infected with a virus, injured by chemicals, or under attack from your own immune system, the basic danger is the same – that your liver will become so damaged that it can no longer work to keep you alive.
Cirrhosis, liver cancer, and liver failure are serious conditions that can threaten your life. Once you have reached these stages of liver disease, your treatment options may be very limited.
That’s why it’s important to catch liver disease early, in the inflammation and fibrosis stages. If you are treated successfully at these stages, your liver may have a chance to heal itself and recover.
Talk to your doctor about liver disease. Find out if you are at risk or if you should undergo any tests or vaccinations.
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.
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