Wolman disease is a form of rare and inherited condition that involves the breakdown and use of cholesterol and fats in the body.
Defining Wolman Disease
Wolman disease is a form of rare and inherited condition that involves the breakdown and use of cholesterol and fats in a person's body or, 'lipid metabolism.' People who are affected by the disease experience harmful amounts of lipids which accumulate in their liver, spleen, small intestine, bone marrow, lymph nodes and adrenal glands. They also experience calcium deposits in their adrenal glands.
When an infant with Wolman disease is born, they are active and healthy. Soon after, they develop signs and symptoms of the disease, which may include:
Poor weight gain
Low muscle tone
Enlarged liver and spleen
Low amounts of iron in the blood
Poor absorption of nutrients from food
A yellow tint to the skin and the whites of the eyes
Children with Wolman disease develop severe malnutrition. Most do not live past early childhood. Wolman disease occurs in approximately one in three hundred and fifty thousand newborns. The disease is also known by the names Acid Lipase Deficiency, Familial Xanthomatosis, Lipa Deficiency LAL deficiency, Liposomal Adic Lipase Deficiency, and Lysomal Acid Lipase Deficiency.
Wolman disease is of a family of disorder referred to as, 'lipid storage diseases.' The disorders are caused by a genetically-inherited defect in one or more enzymes involved in lipid metabolism. The majority of these disorders are, 'autosomal recessive,' meaning both parent have a copy of the gene responsible for the disease and that a child who has been affected by the disease has received the defective gene from each of their parents. Most of the lipid storage diseases are extremely rare in every population.
Causes of Wolman 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.
Wolman disease is caused by mutations in the LIPA gene, which encodes for an enzyme called, 'lysomal acid lipase,' and is found in the lysosomes and breaks down fats such as cholesteryl esters and triglycerides so a persons body may use them. Lysosomes are intracellular structures that digest and recycle substances. Medical science has identified a variety of mutations that lead to defective enzyme activity.
Shortage of lysomal acid lipase leads to an accumulation of cholesteryl esters, triglycerides, as well as other fats within the person's cells. These accumulations, as well as the malnutrition that is caused by the affected persons body's inability to appropriately use lipids, result in the signs and symptoms of Wolman disease. LIPA mutations may also cause cholesteryl ester storage disease, something that is diagnosed later in life and is commonly much less harmful than Wolman disease.
Symptoms of Wolman Disease
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. The symptoms of Wolman disease can appear as quickly as one week after the time a person is born. Potential symptoms include enlarged liver or spleen, vomiting, jaundice, anemia, diarrhea, little or no weight gain, poor muscle tone, developmental delays, and poor absorption of nutrients from food. Babies with Wolman disease are both active and health at birth, yet soon develop signs and symptoms of the disease.
Diagnosing Wolman Disease
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. CT and MRI images may show enlargement of the persons liver or spleen, as well as calcification of both of their adrenal glands, and enlarged lymph nodes.
Treatment of Wolman Disease
A small number of lipid storage disorder are treatable; unfortunately, Wolman disease is not among them and is one that is considered to be a fatal disease of infancy because the majority of children affected by it die during their first year of life. Medical science has not discovered a cure for Wolman disease, and there are no forms of treatments that can reverse the effects of the gene mutation involved. Treatment for the disease involves a focus on management of the persons symptoms, such as malnutrition and anemia.
Intravenous nutritional supplements are one of the most common forms of treatment for Wolman disease; they bypass the persons digestive system. Another form of therapy involves blood transfusions to treat anemia. At this time, there are not specific forms of treatment that can prevent the buildup of lipids in a persons organs. Due to this, some infants with the disease eventually need surgical intervention to remove an enlarged spleen. Should fat deposits reduce their adrenal gland functioning, medications can be administered which may replace the hormones the persons glands would usually secrete.
There is one recorded instance of a person with Wolman disease receiving treatment that provided long-term benefit for them. The treatment this person received was a bone marrow transplant, which caused the disease to enter a remission state. There has yet to be another person who successfully received this form of treatment who has Wolman disease. The success does; however, mean there is potential for bone marrow transplant to become a standard form of treatment for people with the disease.