What are the other Names for this Condition? (Also known as/Synonyms)

• Acid Cholesteryl Ester Hydrolase Deficiency, Wolman type
• LIPA Deficiency
• Liposomal Acid Lipase Deficiency, Wolman Type

What is Wolman Disease? (Definition/Background Information)

• Wolman Disease is a congenital disease characterized by an impaired metabolism of the fats (lipids). It is the most severe type of lysosomal acid lipase deficiency
• The lysomal acid lipase deficiency causes a buildup of lipids (fats) in body organs and calcium deposits in the adrenal glands
• Common symptoms in infants include enlarged liver and spleen, poor weight gain, low muscle tone, jaundice, vomiting, diarrhea, developmental delay, anemia, and poor absorption of nutrients from food
• Wolman Disease is caused by mutations in the LIPA gene, which provides instructions to make the lysosomal acid lipase. Inheritance is autosomal recessive
• The disease is severe and life-threatening, however enzyme replacement therapy, available for the treatment of lysosomal acid lipase deficiencies, in the United States, the European Union, and Japan, have shown improvement of symptoms, including liver problems, as well as an increased life expectancy
• Liver transplantation can be considered in some cases when the liver disease is severe. Reports of treatment with bone marrow transplantation have shown mixed results, correcting the metabolic disease in a few cases, but not in others

(Source: Wolman Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Wolman Disease? (Age and Sex Distribution)

• Wolman Disease is a rare congenital disorder, with a prevalence of less than 10 in a million
• The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Wolman Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since Wolman Disease can be inherited
• Children born to consanguineous parents may be at a higher risk for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Wolman Disease? (Etiology)

• Wolman Disease is caused by mutations in the LIPA gene, which provides instructions to make the lysosomal acid lipase  
• The disease is inherited in an autosomal recessive manner

(Source: Wolman Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Wolman Disease?

The signs and symptoms of Wolman Disease may include the following:

• Abdominal distention
• Adrenal insufficiency
• Anemia
• Ascites
• Adrenal calcification
• Bone-marrow foam cells
• Cachexia
• Cirrhosis
• Esophageal varix
• Fever
• Growth delay
• Global developmental delay
• Hepatic steatosis
• Hepatomegaly
• Malnutrition
• Nausea and vomiting
• Protuberant abdomen
• Steatorrhea
• Splenomegaly

(Source: Wolman Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Wolman Disease Diagnosed?

Wolman Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Wolman Disease?

The complications of Wolman Disease may include:

• Failure to thrive 
• Intestinal malabsorption
• Inadequate weight gain
• Liver failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Wolman Disease Treated?

There is no cure for Wolman Disease, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develop.

• Replacement of the deficiency enzyme has led to moderate improvement in some countries
• Liver transplantation may be recommended, in cases where serious liver damage or liver failure has occurred
• Bone marrow transplantation has shown success in some individuals
• Hematopoietic stem cell transplantation has produced encouraging results in some cases

How can Wolman Disease be Prevented?

Wolman Disease may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Wolman Disease? (Outcomes/Resolutions)

Wolman Disease is a serious and life-threatening disorder, with generally poor outcomes.

• Very few children survive beyond the first year
• Encouraging results have been obtained in some cases with hematopoietic stem cell transplantation
• Typically, the prognosis may be assessed only on a case-by-case basis

Additional and Relevant Useful Information for Wolman Disease:

Wolman Disease is also known as 

• Familial xanthomatosis
• LAL Deficiency, Wolman type

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/