Summary about Disease
Wolman disease (WD) is a rare, autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal acid lipase (LAL) enzyme. This deficiency leads to the accumulation of cholesteryl esters and triglycerides in various organs, primarily the liver, spleen, and adrenal glands. It is the most severe form of lysosomal acid lipase deficiency (LAL-D). WD typically presents in infancy and is characterized by rapid progression, leading to death within the first year of life without treatment.
Symptoms
Failure to thrive
Gastrointestinal issues (vomiting, diarrhea, abdominal distension)
Enlarged liver and spleen (hepatosplenomegaly)
Adrenal gland calcification
Anemia
Jaundice
Developmental delays
Causes
Wolman disease is caused by mutations in the LIPA gene, which provides instructions for making the lysosomal acid lipase (LAL) enzyme. These mutations result in a deficiency or complete absence of functional LAL enzyme. The LAL enzyme is responsible for breaking down cholesteryl esters and triglycerides within lysosomes (cellular compartments that digest and recycle materials). When LAL is deficient, these fats accumulate to toxic levels in cells throughout the body, leading to organ damage and the symptoms of Wolman disease. The condition is inherited in an autosomal recessive manner, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Sebelipase alfa (Kanuma): This enzyme replacement therapy (ERT) is specifically designed to treat LAL-D, including Wolman disease. It provides a functional version of the LAL enzyme, helping to break down the accumulated fats and reduce organ damage.
Is Communicable
No, Wolman disease is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
Since Wolman Disease is genetic, precautions are focused on:
Genetic counseling: Families with a history of Wolman disease should seek genetic counseling to understand the risk of having affected children.
Early diagnosis and treatment: Prompt diagnosis and initiation of enzyme replacement therapy (ERT) with sebelipase alfa can significantly improve outcomes.
Management of symptoms: Supportive care, such as nutritional support and management of gastrointestinal issues, is important to improve the patient's comfort and quality of life.
How long does an outbreak last?
Wolman disease is not an outbreak, it is a chronic, progressive disease. Without treatment, the disease progresses rapidly, and most infants die within the first year of life. With treatment, the progression is slowed, but long-term management is required.
How is it diagnosed?
Enzyme assay: Measuring the activity of the lysosomal acid lipase (LAL) enzyme in blood leukocytes or fibroblasts. A significantly reduced or absent LAL activity is indicative of Wolman disease.
Genetic testing: Analyzing the LIPA gene for mutations. Identification of two disease-causing mutations confirms the diagnosis.
Adrenal gland calcification: X-rays or CT scans may reveal calcification of the adrenal glands, a characteristic feature of Wolman disease.
Liver biopsy: In some cases, a liver biopsy may be performed to assess the extent of fat accumulation and organ damage.
Timeline of Symptoms
Early infancy (within weeks or months of birth): Onset of symptoms such as failure to thrive, vomiting, diarrhea, and abdominal distension.
Progressive organ damage: Enlargement of the liver and spleen (hepatosplenomegaly) develops, leading to anemia, jaundice, and developmental delays.
Adrenal gland calcification: Usually evident within the first few months of life.
Without treatment: Rapid deterioration and death typically occur within the first year of life.
Important Considerations
Early diagnosis is crucial: Prompt diagnosis and initiation of enzyme replacement therapy (ERT) with sebelipase alfa are essential to improve outcomes and prevent irreversible organ damage.
Lifelong treatment: ERT is a lifelong treatment that requires regular infusions.
Monitoring: Regular monitoring of liver function, lipid levels, and other relevant parameters is necessary to assess treatment response and manage potential complications.
Multidisciplinary care: Wolman disease requires a multidisciplinary approach involving specialists in genetics, gastroenterology, hepatology, and other areas to provide comprehensive care.
Family support: Providing support to affected individuals and their families is important to cope with the challenges of living with a rare and serious disease.