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What is AMSD disease?

Published in Genetic Disorders 3 mins read

Acid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease (NPD) type A, type B, or type A/B, is a rare, inherited metabolic disorder affecting the body's ability to break down a fatty substance called sphingomyelin.

Understanding ASMD

ASMD is caused by a deficiency in the enzyme acid sphingomyelinase (ASM). This enzyme is crucial for breaking down sphingomyelin within lysosomes (cellular compartments responsible for waste processing). When ASM is deficient, sphingomyelin accumulates in cells, particularly in the spleen, liver, lungs, bone marrow, and sometimes the brain. This buildup leads to cell damage and organ dysfunction.

Types of ASMD

ASMD is generally classified into different types based on the severity and onset of symptoms:

  • Niemann-Pick Disease Type A (Acute Infantile Form): This is the most severe form, typically appearing in infancy. Infants with Type A have significant neurological involvement, including developmental delays and progressive loss of motor skills. They also experience enlarged organs (hepatosplenomegaly). Life expectancy is typically short, usually within the first few years of life.

  • Niemann-Pick Disease Type B (Chronic Visceral Form): This form is less severe than Type A and typically has a later onset, often in childhood or adolescence. Individuals with Type B generally do not have neurological involvement, but they do experience organ enlargement (especially the spleen and liver) and lung problems. They may also have low platelet counts and elevated lipid levels. Some individuals with Type B can live into adulthood.

  • Niemann-Pick Disease Type A/B: This form represents an intermediate presentation between Type A and Type B, with varying degrees of neurological and visceral involvement.

Symptoms of ASMD

The symptoms of ASMD vary depending on the type and severity of the disease. Common symptoms can include:

  • Enlarged liver and spleen (hepatosplenomegaly)
  • Lung problems (e.g., shortness of breath, frequent infections)
  • Neurological problems (in Type A and some A/B cases): developmental delays, seizures, loss of motor skills
  • Feeding difficulties and failure to thrive (in infants with Type A)
  • Low platelet count (thrombocytopenia)
  • Elevated lipid levels
  • Bone pain
  • Growth retardation

Diagnosis and Treatment

Diagnosis of ASMD typically involves enzyme assays to measure ASM activity in blood cells or fibroblasts. Genetic testing can also be used to confirm the diagnosis and identify specific mutations in the SMPD1 gene (which encodes the ASM enzyme).

Treatment for ASMD is mainly supportive, aiming to manage symptoms and prevent complications. Enzyme replacement therapy (ERT) with olipudase alfa is available for treating the non-neurological manifestations of ASMD (specifically for Type B). Other supportive measures include:

  • Management of lung problems with bronchodilators and oxygen therapy.
  • Blood transfusions to manage low platelet counts.
  • Nutritional support.
  • Physical and occupational therapy.

While there is currently no cure for ASMD, research is ongoing to develop more effective treatments, including gene therapy.

In summary, ASMD is a rare genetic disorder resulting from a deficiency in the enzyme acid sphingomyelinase, leading to the accumulation of sphingomyelin in cells and subsequent organ damage. The different types of ASMD (A, B, and A/B) vary in severity and symptoms.