Wolman disease is a rare, inherited metabolic disorder characterized by the body’s inability to properly break down certain fats. It primarily affects infants, leading to the buildup of fatty substances within various tissues and organs. This accumulation of lipids causes damage, impacting the functioning of several bodily systems shortly after birth.
Genetic Roots and How It Develops
Wolman disease arises from specific changes in the LIPA gene, which produces the lysosomal acid lipase (LAL) enzyme. This enzyme breaks down cholesterol esters and triglycerides within lysosomes, cellular compartments that break down waste. In individuals with Wolman disease, mutations in the LIPA gene lead to an absence of LAL enzyme activity.
Without LAL enzyme activity, cholesterol esters and triglycerides accumulate in various tissues and organs. This buildup is particularly pronounced in organs such as the liver, spleen, and adrenal glands, causing them to enlarge and malfunction. The accumulation of these fats underlies the symptoms observed in affected infants.
Identifying the Manifestations
Infants with Wolman disease begin showing signs within the first few weeks of life. Early symptoms include persistent vomiting and diarrhea, often with failure to gain weight or grow. The abdomen may appear distended due to enlargement of the liver and spleen.
A distinguishing feature is adrenal gland calcification, observable through imaging studies. This calcification, along with severe malnutrition and poor growth, indicates rapid disease progression. Affected infants may also experience developmental regression as the disease advances.
Current Diagnostic Approaches and Care
Diagnosing Wolman disease begins with a clinical assessment based on characteristic infant symptoms, such as abdominal distension and failure to thrive. Imaging studies, like abdominal X-rays, are performed to identify adrenal calcification.
A definitive diagnosis is confirmed by measuring LAL enzyme activity, often using dried blood spots or fibroblast samples. Genetic testing, which involves sequencing the LIPA gene, can further confirm the diagnosis by identifying specific mutations. Current care strategies involve supportive measures like nutritional management to address malabsorption and growth issues.
Enzyme replacement therapy (ERT) with sebelipase alfa (Kanuma) provides the missing LAL enzyme. This medication is administered intravenously and aims to reduce fat accumulation, mitigating organ damage and improving outcomes. Research is ongoing, including clinical trials exploring prenatal ERT to potentially prevent or lessen the disease’s impact before birth.
Life Expectancy and Support
Historically, infants with Wolman disease faced a grim prognosis. Death often occurred within the first year of life, typically by 3 to 6 months, due to severe organ damage and malnutrition.
Enzyme replacement therapy with sebelipase alfa has changed this outlook for some patients, demonstrating improved outcomes and extended survival. While the disease remains severe, ongoing research continues to explore ways to enhance treatment effectiveness and improve long-term prospects. Families affected by Wolman disease can find valuable resources and emotional assistance through various support groups, which offer community and shared experiences.