Wolman disease

Reviewed October 2007

What is Wolman disease?

Wolman disease is a rare inherited condition involving the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of lipids accumulate in the spleen, liver, bone marrow, small intestine, small hormone-producing glands on top of each kidney (adrenal glands), and lymph nodes. In addition to fat deposits, calcium deposits in the adrenal glands are also seen.

Infants with Wolman disease are healthy and active at birth but soon develop signs and symptoms of the disorder. These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia), and poor absorption of nutrients from food. Children affected by this condition develop severe malnutrition and generally do not survive past early childhood.

How common is Wolman disease?

Wolman disease is estimated to occur in 1 in 350,000 newborns.

What genes are related to Wolman disease?

Mutations in the LIPA gene cause Wolman disease.

The LIPA gene provides instructions for producing an enzyme called lysosomal acid lipase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it processes lipids such as cholesteryl esters and triglycerides so they can be used by the body.

Mutations in this gene lead to a shortage of lysosomal acid lipase and the accumulation of triglycerides, cholesteryl esters, and other kinds of fats within the cells and tissues of affected individuals. This accumulation as well as malnutrition caused by the body's inability to use lipids properly result in the signs and symptoms of Wolman disease.

Related Gene(s)

Changes in this gene are associated with Wolman disease.

LIPA

Where can I find information about diagnosis or management of Wolman disease?

These resources address the diagnosis or management of Wolman disease and may include treatment providers.

Genetic Testing Registry: Lysosomal acid lipase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0043208)

You might also find information on the diagnosis or management of Wolman disease in Educational resources (http://www.ghr.nlm.nih.gov/condition/wolman-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/wolman-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Wolman disease?

You may find the following resources about Wolman disease helpful. These materials are written for the general public.

MedlinePlus - Health information
Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/7899/resources/resources/1)
Additional NIH Resources - National Institutes of Health
- National Institute of Neurological Disorders and Stroke: Acid Lipase Disease Information Page (http://www.ninds.nih.gov/disorders/acid_lipase/acid_lipase.htm)
- National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet (http://www.ninds.nih.gov/disorders/lipid_storage_diseases/detail_lipid_storage_diseases.htm)
Educational resources - Information pages
- Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=591)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=75233)
Patient support - For patients and families
CLIMB: Children Living with Inherited Metabolic Diseases (http://www.climb.org.uk/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Lysosomal acid lipase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0043208)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Wolman%20disease%22%20OR%20%22Wolman%20Disease%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Wolman%20Disease%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/278000)

What other names do people use for Wolman disease?

Acid lipase deficiency
Familial Xanthomatosis
LAL deficiency
LIPA deficiency
Liposomal Acid Lipase Deficiency, Wolman Type
Lysosomal acid lipase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Wolman disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Wolman disease?

adrenal glands ; anemia ; bone marrow ; calcium ; cell ; cholesterol ; deficiency ; developmental delay ; enzyme ; familial ; gene ; hepatosplenomegaly ; hormone ; intestine ; iron ; jaundice ; kidney ; lipase ; lipid ; low muscle tone ; lymph ; metabolism ; muscle tone ; triglycerides

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Aslanidis C, Ries S, Fehringer P, Büchler C, Klima H, Schmitz G. Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity. Genomics. 1996 Apr 1;33(1):85-93. (http://www.ncbi.nlm.nih.gov/pubmed/8617513?dopt=Abstract)
Boldrini R, Devito R, Biselli R, Filocamo M, Bosman C. Wolman disease and cholesteryl ester storage disease diagnosed by histological and ultrastructural examination of intestinal and liver biopsy. Pathol Res Pract. 2004;200(3):231-40. (http://www.ncbi.nlm.nih.gov/pubmed/15200275?dopt=Abstract)
Lohse P, Maas S, Sewell AC, van Diggelen OP, Seidel D. Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease. J Lipid Res. 1999 Feb;40(2):221-8. (http://www.ncbi.nlm.nih.gov/pubmed/9925650?dopt=Abstract)
Pagani F, Pariyarath R, Garcia R, Stuani C, Burlina AB, Ruotolo G, Rabusin M, Baralle FE. New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease. J Lipid Res. 1998 Jul;39(7):1382-8. (http://www.ncbi.nlm.nih.gov/pubmed/9684740?dopt=Abstract)
Stein J, Garty BZ, Dror Y, Fenig E, Zeigler M, Yaniv I. Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation. Eur J Pediatr. 2007 Jul;166(7):663-6. Epub 2006 Oct 11. (http://www.ncbi.nlm.nih.gov/pubmed/17033804?dopt=Abstract)
Zschenker O, Jung N, Rethmeier J, Trautwein S, Hertel S, Zeigler M, Ameis D. Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease. J Lipid Res. 2001 Jul;42(7):1033-40. (http://www.ncbi.nlm.nih.gov/pubmed/11441129?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.