Carrier rate:
Estimated at 1 in 50 in Iranian Jews.

Carrier rate in the general population:
Currently unknown

Other ethnic groups in which it occurs:
All ethnic groups with a worldwide incidence of 1 in 350,000.

Inheritance:
Autosomal recessive

Age of onset of symptoms:
Symptoms occur within the first weeks or months of life.

A milder and more benign form of the disease known as Cholesterol Ester Storage Disease may present later in life.

Symptoms:
Wolman disease or lysosomal acid lipase deficiency causes symptoms that are related to the effects of fatty deposits in the persons organs, as well as the their inability to metabolize fats, causing severe malnutrition. Potential symptoms include vomiting, diarrhea, malnourishment, difficulty growing and gaining weight, enlarged liver and spleen (hepatosplenomegaly) which causes a distended abdomen, jaundice, low muscle tone (hypotonia), developmental delays, low blood iron (anemia) and death. X-ray reveals calcified adrenal glands.

Average lifespan:
Almost all die before the age of one.

What causes the features of the disease:
Wolman’s disease is caused by a mutation in a gene called lysosomal acid, lipase A, or LIPA. This gene codes for a protein called lysosomal acid lipase. This protein is an enzyme which plays an instrumental role in breaking down lipids for use or storage. When the gene is defective, the body cannot metabolize certain types of fats. As a result, triglycerides and cholesterol build up within the body and are deposited in the adrenal glands, spleen, liver, intestines, and lymph nodes.

Treatment or management:
There is at present no cure for Wolman disease, so treatment focuses on management of the symptoms. If the adrenal glands are not functioning well, medications can be given to replace the hormones the glands usually make. Nutrition can be given intravenously rather than through the digestive system. Bone marrow transplant and cord blood transplant have been tried as treatments, and possible cures, for Wolman disease.

Carrier testing - number of mutations screened for and detection rate:
Wolman’s disease is caused by a mutation in a gene called lysosomal acid, lipase A, or LIPA. Medical science has identified a variety of mutations that lead to defective enzyme activity. Mutations causing Wolman's disease has been identified in several Iranian Jewish families.

Other testing information:
Carrier testing is available to individuals with a family history of the disease. Testing is available to those with a previously affected child or to couples found to be at risk as carriers.
A definitive diagnosis of Wolman disease is made through a demonstration of deficient lysomal acid lipase activity in the persons white blood cells or, 'fibroblasts,' which are cells that manufacture the supporting matrix of the cell. An amniocentesis may be performed to achieve a prenatal diagnosis of the disease as well. X-ray imaging can present a characteristic pattern of calcification, outlining the outline of the persons cortex of both glands, in enlarged but regularly-shaped adrenal glands.

Current research:
Bone marrow transplant and cord blood transplant have been tried as treatments, and possible cures, for Wolman disease. An infant who received umbilical cord blood from an unrelated donor developed normal levels of lysosomal acid lipase after the transplant, and four years later was thriving.

Researchers are studying the replacement of the deficient enzyme using enzyme replacement therapy (ERT). There are current studies that are studying the ERT for both early onset (Wolman’s Disease) and Late onset (Cholesteryl Ester Storage Disease – CESD). Patients diagnosed with LAL Deficiency, may be eligible for enrollment.

For more information:
Synageva (Biopharmaceutical Company Dedicated to treatment of LAL deficiency)
   www.synageva.com
LAL Solace:
   www.lalsolace.org
LAL Deficiency Source
   www.laldeficiencysource.com
Hide & Seek Foundation for Lysosomal Disease Research:
   www.hideandseek.org
Genetic and Rare Diseases (GARD) Information Center:
   rarediseases.info.nih.gov
Madison's Foundation:
   www.madisonsfoundation.org

For enrollment in the enzyme replacement therapy study email: clinicaltrials@synageva.com
   or go to: Clinical Trials