Wolman Disease - Inheritance and Diagnosis

Inheritance and Diagnosis

What causes Wolman Disease? Every person has two copies of the LAL gene (sometimes known as the LIPA gene). One copy is inherited from the father and one from the mother. LAL Deficiency occurs when a person has defects (mutations) in both copies of the LAL gene. Each parent of a patient with LAL deficiency carries one copy of the defective LAL gene. With every pregnancy, parents with a son or daughter affected by LAL Deficiency have a 1 in 4 (25%) chance of having another affected child. A person born with defects in both LAL genes is not able to produce adequate amounts of the LAL enzyme.
Lysosomes function as recycling centers within cells breaking down unwanted materials into substances that the cells can reuse. The LAL enzyme is responsible for the breakdown of specific fats within the lysosomes. When the lysosome does not have enough LAL enzyme, it is unable to break down these fats.
How common is Wolman Disease? Like many rare diseases, Wolman disease may go undiagnosed or misdiagnosed which means that there is not much information in the medical literature about how common this condition is. Wolman disease affects males and females in equal numbers. In one report, 8 cases of Wolman disease were identified out more than 4.2 million births over the 16-year period. This translates to an incidence around 1 case per 500,000 live births. For a country the size of the United States, this means there may be 8 babies with Wolman disease born each year.
Are there any specific populations that get Wolman disease more frequently than others? Because Wolman disease is autosomal recessive, it is expected to occur at higher frequencies in certain populations where marriages between genetically related individuals occur (consanguinity). A higher frequency of an abnormal LAL gene has been recently described in the Iranian-Jewish population.

A diagnosis of Wolman disease may be suspected in newborn infants based upon identification of characteristic symptoms such as abnormally enlarged liver and gastrointestinal problems.

• A diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history (including family history) and specialized tests that reveal absence or deficient activity of the enzyme lysosomal lipase acid (LIPA) in certain cells and tissues of the body.
• Diagnosis may also be made by confirming that there are mutations (defects) in both copies of the LIPA gene.
• Diagnosis before birth (prenatally) is possible through chorionic villus sampling (CVS) or amniocentesis.
  • During CVS, fetal tissue samples are removed and enzyme tests (assays) are performed on cultured tissue cells (fibroblasts) and/or white blood cells (leukocytes).
  • During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied.