Wolman Disease
What causes someone to have Wolman disease?
Wolman disease is caused by the deficiency of the enzyme lysosomal acid lipase (LAL). LAL is responsible for breaking down certain types of fats, including cholesterol, that occur naturally in the body. When the body does not have enough LAL, these fats build up in the tissues of the body. The progressive build-up of the fats in the organs and tissues cause the symptoms associated with Wolman disease.
Wolman disease is also known as Lysosomal Acid Lipase deficiency and Acid Cholesteryl Ester Hydrolase deficiency, Wolman Type
Are there different types of Wolman disease? How do the types differ?
Wolman disease is one of two diseases that occur when the body makes too little acid lipase. Individuals with Wolman disease have symptoms within the first months of life. The other disease caused by a deficiency of acid lipase is called Cholesteryl Ester Storage disease, or CESD. CESD is a variable condition, which means that different people can have very different experiences with the disease. Some individuals with CESD may not be diagnosed until they reach adulthood.
How common is Wolman disease?
It is estimated that one in every 350,000 newborn babies has Wolman disease. This means that Wolman disease is quite rare.
What are the signs and symptoms of Wolman disease?
Infants with Wolman disease show symptoms within the first weeks or months of life. Parents may note frequent vomiting, watery diarrhea and an enlarged belly.
Infants with Wolman disease "fail to thrive," which means they do not gain weight. The intestines do not work properly and cannot take in calories and nutrients from food, which causes vomiting, diarrhea and severe malnourishment. The malnourishment is caused by an inability to absorb food from the intestine into the body. Infants will have an enlarged liver and spleen (hepatosplenomegaly), which causes the abdomen to appear swollen and distended. The enlarged liver and spleen and distended abdomen can cause an umbilical hernia (hernia of the belly button). Infants with Wolman disease have hypotonia (low muscle tone) and delayed development of motor skills, which are probably caused by malnutrition. Blood tests may show anemia. An X-ray or CT scan may show calcifications in the adrenal glands, which means that the adrenal glands may appear unusually bright compared to other soft body organs and tissues. The adrenal glands may not make enough of the essential adrenal hormones and steroids. This deficiency of adrenal steroids can affect metabolism, blood pressure and the immune system. A bone marrow sample may show unusual, large, fat-filled cells called "foamy histocytes."
Infants with Wolman disease usually die during the first year of life. Death is often due to complications of malnourishment and deficiency of adrenal function.
How is Wolman disease diagnosed?
A doctor may suspect Wolman disease based on an infant's symptoms or family history. However, one specific test must be ordered to confirm a diagnosis of Wolman disease. Because Wolman disease occurs when the body does not make enough lysosomal acid lipase, the test measures the amount of lysosomal acid lipase in blood or skin cells. Cells from a person with Wolman disease will have less than 10 percent the usual amount of lysosomal acid lipase.
Prenatal testing for Wolman disease during pregnancy is possible. Amniocentesis can be performed and cells from the amniocentesis sample can be grown in the laboratory and tested.
What kinds of treatment are available for individuals with Wolman disease?
There is no cure for Wolman disease at this time. If the adrenal gland is not making enough hormones and steroids, medications can be given to replace the missing compounds in the body. Nutrition can be given intravenously (by IV).
Is research being done on Wolman disease?
The Cincinnati STAR Center for Lysosomal Diseases is one of the only groups in the world researching Wolman disease and cholesteryl ester storage disease (CESD), a related disorder. In order to understand how these diseases affect the human body, genetic techniques are used to create a mouse model for Wolman disease and cholesteryl ester storage disease. A "mouse model" is a mouse that has genetic changes and physical symptoms that resemble those seen in people affected with these conditions. Research is focused on the efficacy of enzyme replacement therapy and gene therapy in this mouse model of lysosomal acid lipase deficiency. The studies include the dose, effect and safety of the enzyme replacement therapy on the mouse model. The data collected from these studies is critical for the next step of research, which will be clinical research on treatment of Wolman disease and cholesteryl ester storage disease by enzyme replacement therapy.
The National Institutes of Health (NIH) maintains a web site that lists many clinical trials recruiting participants in the United States. To search for clinical trials, visit www.clinicaltrials.gov
Where can I go to get more information on Wolman disease?
Cincinnati STAR Center for Lysosomal Diseases
Telephone: 1-800-647-4805
Fax: 513-636-0124
Mail: Cincinnati STAR Center for Lysosomal Diseases
C / o Debbie Baker
Cincinnati Children's Hospital Medical Center
Division of Human Genetics
3333 Burnet Avenue ML 4006
Cincinnati, OH 45229
The National Organization for Rare Disorders (NORD) is an organization dedicated to helping people with rare diseases. NORD works toward diagnosing, treating and curing rare disorders through programs of education, advocacy, research and service. http://www.rarediseases.org/
Written 2/05
