Longevity logo

What is Wolman Disease?

healthcare services

By haven smithPublished 3 years ago 3 min read
Like
Wolman Disease Market

Wolman disease is a type of lysosomal acid lipase (LAL) deficiency inherited as an autosomal recessive trait resulting in the deposition of fats in multiple organs. It is the most severe expression of LAL deficiency. Wolman disease is caused by mutations in the lysosomal acid lipase (LIPA) gene. This enzyme is essential for metabolizing certain fats in the body, without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Mutations 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 due to which the LDL triglycerides and cholesteryl esters that enter the cells cannot be hydrolyzed.

The symptoms of Wolman disease usually become apparent shortly after birth, during the first few weeks of life. Affected infants may develop bloating or swelling of the stomach (abdominal distention) and may have significant enlargement of the liver and spleen (hepatosplenomegaly). Scarring (fibrosis) of the liver may also occur. In some cases, fluid may accumulate in the abdominal cavity (ascites).

Infants with Wolman disease have serious digestive abnormalities, including malabsorption. Malabsorption associated with Wolman disease causes persistent and often forceful vomiting, frequent diarrhea, foul-smelling, steatorrhea and malnutrition. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age.

The condition is diagnosed by enzymatic assay in fibroblasts and lymphocytes and is confirmed by mutational analysis of the lipase A, lysosomal acid, and cholesterol esterase (LIPA) gene. There is no definitive treatment available for Wolman disease, and death is usually within the first year of life (median age of death according to the recently presented natural history data is 3.4 months).

Lysosomal storage diseases (LSDs) as a group of diseases can lead to a wide array of clinical presentations and underlying cellular phenotypes depending on the nature of the macromolecule accumulated. As per National Organization for Rare Disorders, Wolman disease is an extremely rare disorder that affects males and females in equal numbers. More than 50 cases have been reported in the medical literature. However, cases may go undiagnosed or misdiagnosed making it difficult to determine.

The defect in Wolman's disease is in the LIPA gene which is located on chromosome 10q23.2–q23.3 and comprises 10 exons; mutations of which result in the deficiency of LAL. Several mutations have been identified, some of which lead to almost complete loss of enzyme activity with early presentation, which is the typical phenotype of Wolman's disease; whereas others cause only a partial disruption of the enzyme activity leading to a clinically more benign condition called cholesteryl ester storage disease (CESD), the onset of which is later on in life.

Infants with Wolman disease may experience the loss of previously acquired skills required for the coordination of muscle and motor skills (psychomotor regression). The symptoms of Wolman disease often become progressively worse, eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), 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).

There are no formal guidelines for the treatment of these patients, and treatment options are limited. Early-onset Wolman disease presents shortly after birth and is rapidly fatal within the first year of life with severe malabsorption, growth failure and liver failure. Unfortunately, there are no forms of treatments that can reverse the effects of the gene mutation involved. Treatment for the disease involves a focus on the management of the symptoms, such as malnutrition and anemia.

Compared with ERT, small-molecule based therapies hold several advantages. First, small-molecule drugs can be taken orally by patients, whereas ERT requires intravenous administration during lengthy clinic visits. Second, small-molecule drugs can be optimized to penetrate into various tissues, including CNS, while ERT is only useful for treatments of peripheral symptoms. Lastly, the astronomically high cost of ERT is a tremendous burden for patients. In addition, a combination of both small molecule therapy and ERT could be synergistic, thus reducing the need for frequent dosing for ERT and improving the therapeutic effects.

Original Source:- Wolman Disease Market

health
Like

About the Creator

haven smith

https://www.delveinsight.com/

Reader insights

Be the first to share your insights about this piece.

How does it work?

Add your insights

Comments

There are no comments for this story

Be the first to respond and start the conversation.

Sign in to comment

    Find us on social media

    Miscellaneous links

    • Explore
    • Contact
    • Privacy Policy
    • Terms of Use
    • Support

    © 2024 Creatd, Inc. All Rights Reserved.