Wolman Disease

Inherited storage disorder

Wolman disease is an inherited fat storage disorder of chromosome 10 caused by deficiency of the enzyme lysosomal acid lipase in the body. Without the enzyme, fats, including cholesterol, build up in the body tissues and become toxic. Wolman disease is very rare, with only 50 reports of the disease published in the worldwide medical literature. It affects both males and females and is inherited in an autosomal recessive manner, meaning that a child must inherit two copies of the defective gene, one from each parent, in order to develop the disorder.

Some individuals who have a deficiency of lysosomal acid lipase have a less severe disorder than Wolman disease called cholesteryl ester storage disease, which may not be diagnosed until adulthood.

Symptoms
Since Wolman disease is inherited, infants are born with the disorder, and begin to show symptoms within the first weeks or months of life. Symptoms may include:

• vomiting, diarrhea
• malnourishment, difficulty growing and gaining weight
• enlarged liver and spleen (hepatosplenomegaly), which causes a distended abdomen
• low muscle tone (hypotonia)
• low blood iron (anemia)
• x-ray reveals calcified adrenal glands

Diagnosis
The symptoms the infant is experiencing, and the presence of calcified adrenal glands, will suggest the diagnosis of Wolman disease. A blood sample or skin sample (biopsy) is tested for the level of lysosomal acid lipase present. Samples from an infant with Wolman disease will show less than 10 percent of the normal level, and confirm the diagnosis.

Treatment
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.

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 also studying replacing the deficient enzyme through gene therapy in mice with cholesteryl ester storage disease.

Sources:
- Stein, J., B. Zion Garty, Y. Dror, E. Fenig, M. Ziegler, & I. Yaniv. "Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation." Eur J Pediatr (2006).
- Vanier, Dr. M.T.. "Wolman Disease." OrphaNet. Jan 2007. OrphaNet. 16 Mar 2007 <http://www.orpha.net/consor/cgi-bin/data.php?ActType=Pat&Form=Pat&PatId=11067>.
- "Wolman Disease." Lysosomal Disease Health Information. Feb 2005. Cincinnati Children's Hospital Medical Center. 16 Mar 2007 <http://www.cincinnatichildrens.org/svc/alpha/l/lysosomal/health/wolman-disease.htm>.