Summary about Disease
Lysosomal acid lipase deficiency (LAL-D) is a rare, inherited metabolic disorder characterized by the buildup of fatty substances in cells throughout the body. This buildup occurs because the body doesn't produce enough of an enzyme called lysosomal acid lipase (LAL), which is needed to break down fats and cholesterol. LAL-D exists on a spectrum, with two main presentations: Wolman disease, the severe infantile form, and cholesteryl ester storage disease (CESD), a later-onset, milder form. Both forms lead to liver damage, elevated cholesterol, and other health complications.
Symptoms
Wolman disease (infantile):
Failure to thrive
Enlarged liver and spleen (hepatosplenomegaly)
Gastrointestinal problems (vomiting, diarrhea)
Calcification of the adrenal glands
Anemia
Cholesteryl ester storage disease (CESD):
Elevated cholesterol and triglycerides
Enlarged liver (hepatomegaly)
Abnormal liver function tests
Fatty liver (hepatic steatosis)
Fibrosis or cirrhosis of the liver (in some cases)
Premature cardiovascular disease
Abdominal pain
Growth retardation (in children)
Causes
LAL-D is caused by mutations in the LIPA gene, which provides instructions for making the lysosomal acid lipase (LAL) enzyme. These mutations lead to a deficiency or complete absence of the LAL enzyme, preventing the proper breakdown of fats and cholesterol within lysosomes (cellular compartments). It is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.
Medicine Used
Sebelipase alfa (Kanuma): Enzyme replacement therapy that provides a functional version of the LAL enzyme. This helps to break down the accumulated fats and cholesterol, reducing the symptoms and complications of LAL-D. It is approved for use in both children and adults with LAL-D.
Statins: To manage high cholesterol levels.
Other supportive medications: To manage specific symptoms, such as liver complications.
Is Communicable
No, LAL-D is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Genetic counseling: Important for families with a history of LAL-D to understand the risk of inheriting the condition.
Regular monitoring: Patients with LAL-D need regular monitoring of liver function, cholesterol levels, and overall health.
Adherence to treatment: Following the prescribed medication regimen, particularly enzyme replacement therapy, is crucial for managing the disease.
Lifestyle modifications: A healthy diet and lifestyle can help to manage cholesterol levels and support liver health.
How long does an outbreak last?
LAL-D is not an infectious disease with outbreaks. It is a chronic, progressive disorder that persists throughout a person's lifetime. Symptoms may worsen over time if left untreated.
How is it diagnosed?
Enzyme assay: Measures the activity of the LAL enzyme in blood samples (e.g., dried blood spot testing or leukocytes). Low or absent LAL activity indicates LAL-D.
Genetic testing: Identifies mutations in the LIPA gene to confirm the diagnosis.
Liver biopsy: May be performed to assess the extent of liver damage and to look for characteristic features of LAL-D.
Lipid profile: Measures cholesterol and triglyceride levels, which are often elevated in LAL-D.
Imaging studies: Ultrasound, CT scan, or MRI may be used to assess the size and condition of the liver and spleen.
Timeline of Symptoms
Wolman disease: Symptoms typically appear within the first few months of life. Rapid progression leads to death within the first year if untreated.
CESD: Symptoms may appear in childhood or adulthood. The progression of the disease is slower than in Wolman disease, but liver damage and cardiovascular complications can develop over time. The timeline varies among patients.
Important Considerations
Early diagnosis is crucial: Early diagnosis and treatment with enzyme replacement therapy can significantly improve outcomes for individuals with LAL-D.
Multidisciplinary care: Management of LAL-D requires a team of specialists, including gastroenterologists, hepatologists, geneticists, and cardiologists.
Long-term management: LAL-D is a chronic condition that requires ongoing monitoring and management.
Newborn screening: Consideration is being given to including LAL-D in newborn screening programs to facilitate early diagnosis.
Support groups: Support groups can provide valuable emotional support and information for patients and families affected by LAL-D.