Last updated:
9/9/2025
Years published: 2009, 2012, 2015, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Jakub Tolar, MD, PhD, Tulloch Chair in Stem Cell Biology, Genetics and Genomics, Director, Stem Cell Institute, Professor, Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, for assistance in the preparation of this report.
Summary
Wolman disease is a type of lysosomal acid lipase (LAL) deficiency, a rare genetic disorder characterized by complete absence of an enzyme known as lysosomal acid lipase (LIPA or LAL). This enzyme is required to break down (metabolize) certain fats (lipids) in the body. Without the LIPA enzyme, certain fats may abnormally accumulate in the tissues and organs of the body causing a variety of symptoms. Wolman disease may cause bloating or swelling of the stomach (abdominal distention), vomiting and significant enlargement of the liver or spleen (hepatosplenomegaly). Life-threatening complications often develop during early childhood. Wolman disease is caused by changes (variants) in the lysosomal acid lipase (LIPA) gene and is inherited in an autosomal recessive pattern.
In 2015, the U.S. Food and Drug Administration (FDA) approved Kanuma (sebelipase alfa) as the first treatment for people with LAL deficiency.
Introduction
Wolman disease is the most severe expression of LAL deficiency. A milder form of LAL deficiency is known as cholesteryl ester storage disease (CESD). LIPA gene variants that cause CESD result in some enzyme activity, whereas LIPA gene variants that cause Wolman disease produce an enzyme with no residual activity or no enzyme at all. Genetic and biochemical evidence indicates that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.
Wolman disease is named after one of the doctors who first reported the disorder in the medical literature in 1956.
Signs & Symptoms
The symptoms of Wolman disease usually become apparent shortly after birth, usually during the first few weeks of life. Signs and symptoms may include:
Additional symptoms may also occur in Wolman disease including yellowing of the skin, mucous membranes and whites of the eyes (jaundice), a persistent low-grade fever and poor muscle tone (hypotonia). Infants may have delays in the development of motor skills.
A distinct finding associated with Wolman disease is the hardening of adrenal gland tissue due to the accumulation of calcium (calcification). The adrenal glands are located on top of the kidneys and produce two hormones called epinephrine and norepinephrine. Other hormones produced by the adrenal glands help to regulate the fluid and electrolyte balance in the body. Calcification of the adrenal glands is not detectable by physical examination but can be seen with an X-ray. Calcification may prevent the adrenal glands from producing enough essential hormones and can affect metabolism, blood pressure, the immune system and other vital processes of the body.
Infants with Wolman disease may experience the loss of previously acquired skills required the coordination of muscle and motor skills (psychomotor regression). The symptoms of Wolman disease often get progressively worse eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), liver (hepatic) dysfunction or failure, and physical wasting away and severe weakness often associated with chronic disease and marked by weight loss and loss of muscle mass (cachexia or inanition).
Wolman disease is caused by variants in the lysosomal acid lipase (LIPA) gene. The LIPA gene contains instructions for producing the enzyme lysosomal acid lipase. This enzyme is essential for breaking down (metabolizing) certain fats in the body, especially cholesterol (specifically cholesteryl esters) and to a lesser degree triglycerides. Without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Variants in the LIPA gene that cause Wolman disease result in the lack of production of the LIPA enzyme or production of a defective, inactive form of the LIPA enzyme.
Wolman disease is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Wolman disease affects less than 1 in 100,000 newborns. As of 2025, estimates from the medical literature suggest that about 71 cases of Wolman disease have been reported globally, and it affects males and females in equal numbers. However, cases may go undiagnosed or misdiagnosed making it difficult to determine the true frequency of this condition in the general 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. Molecular genetic testing for variants in the LIPA gene is also available to confirm the diagnosis.
Treatment
In 2015, the U.S. Food and Drug Administration (FDA) approved the enzyme replacement therapy (ERT) sebelipase alfa (Kanuma) as the first treatment for people with LAL deficiency. This intravenous treatment replaces the missing or malfunctioning enzyme, helping cells break down accumulated substances and significantly improving survival, growth and biological markers for affected infants and children. While effective, ERT can have limitations, including the potential for the body to develop antibodies against the enzyme and challenges in addressing brain involvement due to the blood-brain barrier.
Other treatment is directed toward the specific symptoms that are apparent in each individual. A team approach for individuals with Wolman disease may be necessary and may include special social support and other medical services. Genetic counseling is recommended for affected individuals and their families.
Proper nutrition can be maintained intravenously. If the adrenal glands are not functioning properly, medications may be used to supplement the hormones normally produced by these glands.
According to the medical literature, a few children with Wolman disease have been treated with hematopoietic stem cell transplantation (HSCT). Hematopoietic stem cells are specialized cells found in bone marrow (the soft spongy material found in long bones). These blood stem cells grow and eventually develop into one of the three main types of blood cells– red blood cells, white blood cells or platelets. A transplant is done to replace the bone marrow (and consequently the whole blood system) of an affected individual with marrow from a person who does not have a particular disorder. The healthy cells produced by the new marrow contain sufficient levels of lysosomal acid lipase required to break down cholesterol and triglycerides. People with Wolman disease treated with HSCT have shown dramatic improvement in existing symptoms and avoidance of additional complications such as liver failure. Researchers speculate that early diagnosis and prompt treatment with HSCT increases the chance of preserving liver function and preventing cognitive decline. More research is necessary to determine the long-term safety and effectiveness of this potential therapy for infants with Wolman disease. Hematopoietic stem cell transplants are not without drawbacks. The procedure is expensive and carries the risk of serious complications including graft-versus-host disease and other long-term and late effects.
Gene therapy is also being studied as a possible approach to therapy for some lysosomal storage disorders.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOK
Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:3551-3572.
JOURNAL ARTICLES
de Castro MJ, Jones SA, de las Heras J, et al. Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease. Orphanet J Rare Dis. 2024;19:244. https://doi.org/10.1186/s13023-024-03219-5
Nedelcu C, Dijmarescu I, Patrascoiu M, Oprescu I, Pacurar D. Lysosomal Acid Lipase Deficiency: A Report of Two Cases and a Review of the Literature. Cureus. 2024;16(11):e73299. Published 2024 Nov 8. doi:10.7759/cureus.73299
Potter JE, Petts G, Ghosh A, et al. Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease. Orphanet J Rare Dis. 2021;16(1):235. Published 2021 May 21. doi:10.1186/s13023-021-01849-7
Tolar J, Petryk A, Khan K, et al. Long-term metabolic, endocrine, and neuropsychological outcome of hematopoietic cell transplantation for Wolman disease. Bone Marrow Transplant. 2009;43(1):21-27. doi:10.1038/bmt.2008.273
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;200:231-240.
Krivit W, Peters C, Dusenbery K, et al. Wolman disease successfully treated by bone marrow transplantation Bone Marrow Transplantation. 2000;26:567-570.
Pagani F, Pariyarath R, Garcia R, et al. New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease. J Lipid Res. 1998;39:1382-1388.
INTERNET
Wolman Disease. Orphanet. April 2020. Available at: https://www.orpha.net/en/disease/detail/75233 Accessed Sept 8, 2025.
Wolman disease. McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 278000; Last Update: 07/28/2023. Available at: https://omim.org/entry/620151 Accessed Sept 8, 2025.
Wilson DP, Patni N. Lysosomal Acid Lipase Deficiency. [Updated 2023 Mar 15]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK395569/ Accessed Sept 8, 2025.
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View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View reportGeneReviews has an article on this condition covering diagnosis, management, and inheritance. Each article is written by one or more experts on the specific disease and is reviewed by other specialists. The article contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. The GeneReviews database is managed by the University of Washington.
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