LAL deficiency

LAL Deficiency Lysosomal Acid Lipase (LAL) Deficiency is a rare genetic disorder that affects the body's ability to break down certain fats (lipids). This condition is caused by mutations in the LIPA gene, which leads to a deficiency of the enzyme lysosomal acid lipase. This enzyme is crucial for the breakdown of cholesteryl esters and triglycerides within the lysosomes.

Pathophysiology

LAL deficiency results in the accumulation of lipids in various tissues and organs, including the liver, spleen, and blood vessels. This accumulation can lead to a range of symptoms and complications, depending on the severity of the enzyme deficiency.

• LIPA Gene

The LIPA gene provides instructions for making the lysosomal acid lipase enzyme. Mutations in this gene reduce or eliminate the activity of the enzyme, leading to the accumulation of lipids.

Types of LAL Deficiency

LAL deficiency is categorized into two main types based on the severity and age of onset:

• Wolman Disease

Wolman disease is the more severe form of LAL deficiency, typically presenting in infancy. It is characterized by rapid progression and severe symptoms, including: - Hepatomegaly (enlarged liver) - Splenomegaly (enlarged spleen) - Failure to thrive - Vomiting and diarrhea - Adrenal calcification

• Cholesteryl Ester Storage Disease (CESD)

CESD is a milder form of LAL deficiency that can present at any age, from childhood to adulthood. Symptoms may include: - Hepatomegaly - Elevated liver enzymes - Hyperlipidemia (high levels of fats in the blood) - Atherosclerosis

Diagnosis

Diagnosis of LAL deficiency involves a combination of clinical evaluation, biochemical tests, and genetic testing. Key diagnostic methods include: - Measurement of lysosomal acid lipase activity in leukocytes or fibroblasts - Genetic testing for mutations in the LIPA gene - Liver biopsy to assess lipid accumulation

Treatment

Treatment options for LAL deficiency are limited but may include: - Enzyme replacement therapy (ERT) with sebelipase alfa, which can help reduce lipid accumulation and improve liver function - Supportive care to manage symptoms and complications - Dietary modifications to reduce fat intake

Prognosis

The prognosis for individuals with LAL deficiency varies depending on the type and severity of the condition. Wolman disease has a poor prognosis, with most affected infants not surviving beyond the first year of life. CESD has a more variable prognosis, with some individuals living into adulthood with appropriate management.

Research and Future Directions

Ongoing research aims to improve the understanding of LAL deficiency and develop new treatments. Gene therapy and other novel approaches are being explored as potential future therapies.

See Also

• Lysosomal Storage Disorders
• Genetic Disorders
• Enzyme Replacement Therapy

NIH genetic and rare disease info

• NIH info on LAL deficiency

LAL deficiency is a rare disease.