Synageva BioPharma Corp. is recruiting patients to participate in global clinical trials that evaluate sebelipase alfa (SBC-102) as an enzyme replacement therapy for Lysosomal Acid Lipase (LAL) Deficiency. For more information, please visit clinicaltrials.gov, or click here if you would like to contact Synageva regarding LAL Deficiency.


Lysosomal Acid Lipase (LAL) Deficiency

Lysosomal Acid Lipase (LAL) Deficiency belongs to a family of diseases called Lysosomal Storage Disorders (LSDs). These are inherited genetic conditions, and like some other genetic diseases such as cystic fibrosis, parents may not know they are carriers for the disease until they have a child who is born with the condition. When both parents are carriers, there is a one in four chance that their baby will be born without the ability to produce the lysosomal acid lipase (LAL) enzyme. The LAL enzyme breaks down fatty material (cholesteryl esters and triglycerides), and the lack of the LAL enzyme results in a build-up of these materials in the liver, the gut or other important organs including the walls of blood vessels. LAL Deficiency occurs less frequently in infants than it does in children, adolescents or adults. Infants presenting with LAL Deficiency, sometimes called Wolman disease, is rapidly fatal, usually within the first six months of life. LAL Deficiency in children and adults, sometimes called Cholesteryl Ester Storage Disease (CESD), may lead to liver fibrosis, cirrhosis, liver failure and premature death. Also, there may be an increased risk of cardiovascular events.

LAL Deficiency is sometimes called:

  • Acid Cholesteryl Ester Hydrolase Deficiency, Type 2
  • Acid Lipase Disease
  • Cholesteryl Ester Hydrolase Deficiency Storage Disease
  • Cholesterol Ester Storage Disease or CESD
  • Wolman disease

Related disorders may include:

  • Non-Alcoholic Fatty Liver Disease (NAFLD)
  • Non-Alcoholic Steatohepatitis (NASH)
  • Alcoholic Liver Disease
  • Cryptogenic Cirrhosis
  • Niemann-Pick Disease (NPD) Type C
  • Chanarin Dorfman Syndrome 


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What is a Lysosomal Storage Disorder (LSD)?

Lysosomal Acid Lipase (LAL) Deficiency belongs to a family of diseases called Lysosomal Storage Disorders. Lysosomes are found in the body’s cells and play an important role in digesting nutrients and other materials. LSDs are inherited conditions in which one or more of the enzymes in lysosomes is missing or not functioning effectively. When this happens, materials that would normally be broken down by the lysosome accumulate and this disturbs normal cell function.

For more information on Lysosomal Storage Disorders and inheritance, watch this video from the Hide and Seek Foundation (narrated by Alec Baldwin).


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What is LAL Deficiency?

Under normal conditions, the body produces an enzyme called lysosomal acid lipase (LAL). The LAL enzyme breaks down fatty material (cholesteryl esters and triglycerides). Lysosomal Acid Lipase (LAL) Deficiency happens when the body is not producing enough LAL. Infants, children and adults that suffer from LAL Deficiency experience a range of very serious and devastating health problems. The lack of the LAL enzyme results in a build-up of fatty material in the liver, spleen and blood vessels. In some patients this build-up also occurs in the gut and other important organs or places within the body.

Infants presenting with LAL Deficiency, which is sometimes called Wolman disease after Moshe Wolman, the physician who first described it, is almost universally fatal within the first six months of life.

To see the story about Dakota Dykes' battle with the infant form of LAL Deficiency (Wolman disease), follow this link: http://www.wfaa.com/news/health/NORTH-TEXAS-BABY-BATTLES-RARE-DISEASE-78462787.html

LAL Deficiency in children and adults is sometimes called Cholesteryl Ester Storage Disease (CESD). Patients experience a build up of fatty material mostly in the liver and blood vessel walls although other body organs may be affected too. The build up of fatty material in the liver cells may lead to an oversized liver, cirrhosis and chronic liver failure.

LAL Deficiency is a serious and life-threatening disease, and there are no approved treatments. Synageva BioPharma Corp. is recruiting patients to participate in a clinical trial that evaluates sebelipase alfa as an enzyme replacement therapy of Lysosomal Acid Lipase (LAL) Deficiency. For more information, please visit clinicaltrials.gov, or click here if you would like to contact Synageva regarding LAL Deficiency.


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How does a person get LAL Deficiency?

LAL Deficiency is an inherited condition. The gene that is responsible for telling the body how to make the LAL enzyme is not normal, and the LAL enzyme either does not work properly or is not made at all. Every person inherits two copies of the LAL gene: one copy from the mother and the other from the father. A person with LAL Deficiency has inherited one faulty copy of the gene from the mother and one faulty copy of the gene from the father. Having only one copy of the faulty gene does not usually lead to the disease, although the person with one copy of the faulty gene becomes a carrier of the disease and can pass on the faulty copy to their children. When both parents are carriers, there is a 25% (one in four) chance with each pregnancy that their child will have LAL Deficiency.


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How is LAL Deficiency diagnosed?

Abnormalities that you may have, and that would make your doctor think of LAL Deficiency includes:

  • Increases in liver enzymes (transaminases: AST and ALT)
  • A high cholesterol and high triglyceride level  
  • A high 'bad' cholesterol (LDL)
  • A very low 'good' cholesterol (HDL)
  • A larger than normal liver due to fat accumulation

LAL Deficiency is often unrecognized because many physicians have not had experience with this condition. The diagnosis begins with your physician taking an interview and history, conducting an examination and ordering preliminary lab tests. Your physician may look for or ask about the following liver conditions:

  • Unexplained hepatomegaly (liver enlargement)
  • Elevated liver enzymes (a marker of liver damage)
  • Unexplained fat or lipid material in the liver
  • Unexplained chronic liver disease that may be getting worse over time

Some common diseases that resemble LAL Deficiency and may lead to a missed diagnosis are:

  • Infectious causes such as viral hepatitis
  • Metabolic Causes such as Non Alcoholic Fatty Liver Disease (NAFLD) or Non Alcoholic Steatohepatitis (NASH)
  • Autoimmune liver disease (where the body's immune system damages liver cells)

Other clues that may help your physician make the diagnosis of LAL Deficiency are:

  • Low normal HDL, especially very low HDL
  • Short stature
  • Enlarged lymph nodes
  • An enlarged spleen

These observations are less common in patients with other liver diseases and, therefore, are important clues that may point your physician to a diagnosis of LAL Deficiency.

Once your physician thinks about the possibility of LAL Deficiency as a cause of your medical problems, he or she may order a confirmatory test such as an enzyme assay (leukocyte or a dried blood spot) or a genetic sequencing analysis. The enzyme assay measures the level and activity of the LAL enzyme or genetic sequencing helps to identify whether you have a genetic mutation that is consistent with LAL Deficiency.  LAL Deficiency is a progressive disease that results in damage to the liver, spleen and other internal organs. LAL Deficiency potentially leads to fibrosis, cirrhosis, liver failure and death. An accurate diagnosis is the first step toward getting control over the serious long term and often life-threatening complications of this disease.


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How is LAL Deficiency treated?

There are no approved treatments for LAL Deficiency. However, Synageva BioPharma Corp. is recruiting patients to participate in a clinical trial that evaluates sebelipase alfa as the first enzyme replacement therapy for Lysosomal Acid Lipase (LAL) Deficiency. Enzyme replacement therapies have been used successfully for other lysosomal storage disorders. For more information, please visit clinicaltrials.gov, or click here if you would like to contact Synageva regarding LAL Deficiency.

For children and adults with LAL Deficiency (CESD), the physician may prescribe cholesterol-lowering drugs (‘statins’ and/or ezetimibe) because of the high levels of cholesterol and other fats in the blood (high ‘bad‘ cholesterol (LDL)). Although these drugs can reduce serum cholesterol levels to some extent, they have not been shown to improve the underlying disease and the severe liver manifestations. Also, some evidence exists that these drugs may actually hide the disease progression.

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