Summary about Disease
Acid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease type A and B, is a rare, inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase (ASM). This enzyme is crucial for breaking down sphingomyelin, a fatty substance present in every cell of the body. When ASM is deficient, sphingomyelin accumulates in cells, particularly in the spleen, liver, lungs, and bone marrow. This accumulation leads to cellular dysfunction and organ damage. The severity of ASMD varies; type A is a severe, infantile-onset form, while type B is a less severe, later-onset form.
Symptoms
Symptoms vary depending on the type and severity of ASMD.
Type A (Infantile-onset): Feeding difficulties, failure to thrive, enlarged liver and spleen (hepatosplenomegaly), progressive neurological deterioration, cherry-red spot in the eye, intellectual disability, lung problems, and enlarged abdomen.
Type B (Later-onset): Enlarged liver and spleen (hepatosplenomegaly), lung problems (e.g., shortness of breath, recurrent respiratory infections), low platelet count (thrombocytopenia), high cholesterol levels, skeletal problems, and corneal clouding. Neurological involvement is typically absent or milder than in type A.
Causes
ASMD is caused by mutations in the SMPD1 gene. This gene provides instructions for making the acid sphingomyelinase enzyme. These mutations result in a deficiency or absence of functional ASM. The disease is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Olipudase alfa (Xenpozyme): This is an enzyme replacement therapy (ERT) approved for the treatment of non-central nervous system manifestations of ASMD type B and some people with ASMD type A. It replaces the missing or deficient ASM enzyme, helping to break down sphingomyelin.
Supportive therapies: Treatment focuses on managing the symptoms of ASMD. This may include medications to manage lung problems, blood transfusions for thrombocytopenia, cholesterol-lowering medications, and nutritional support.
Bone marrow transplantation/Hematopoietic stem cell transplantation (HSCT): In some cases, particularly for type B, HSCT has been considered, although the efficacy is variable.
Is Communicable
No. ASMD is not communicable. It is a genetic disorder, not an infectious disease. It cannot be spread from person to person.
Precautions
Genetic counseling: Families with a history of ASMD should consider genetic counseling to understand their risk of having a child with the disease.
Carrier testing: Individuals can undergo carrier testing to determine if they carry a copy of the mutated SMPD1 gene.
Management of symptoms: Precautions are focused on managing the specific symptoms of the disease, such as avoiding lung irritants, managing cholesterol levels, and preventing bleeding due to thrombocytopenia.
How long does an outbreak last?
ASMD is not an infectious disease and does not have "outbreaks." It is a chronic, progressive genetic disorder. The symptoms persist throughout the affected individual's life, although the severity and progression can vary.
How is it diagnosed?
Enzyme assay: Measures the level of ASM activity in blood cells (leukocytes) or cultured skin cells (fibroblasts). Low or absent ASM activity indicates ASMD.
Genetic testing: Sequencing of the SMPD1 gene to identify mutations. This can confirm the diagnosis and help determine the specific type of ASMD.
Bone marrow aspiration: May be performed to assess the presence of lipid-laden macrophages (foam cells), which are characteristic of ASMD.
Liver biopsy: Can show sphingomyelin accumulation in liver cells.
Chest X-ray or CT scan: To evaluate lung involvement.
Eye exam: To look for cherry-red spot or corneal clouding.
Timeline of Symptoms
Type A: Symptoms typically appear in the first few months of life. Progressive neurological decline, hepatosplenomegaly, feeding difficulties, and failure to thrive are common early features.
Type B: Symptoms can appear in childhood or adulthood. Hepatomegaly and/or splenomegaly are often the first signs, followed by lung problems, low platelet counts, and other symptoms. The timeline of symptom onset and progression varies considerably among individuals with type B.
Important Considerations
Early diagnosis: Early diagnosis is crucial for initiating appropriate management and supportive care.
Multidisciplinary care: Management of ASMD requires a multidisciplinary team of specialists, including geneticists, pulmonologists, gastroenterologists, hematologists, and neurologists.
Family support: ASMD can be a challenging disease for both patients and their families. Support groups and counseling can provide valuable assistance.
Research: Ongoing research is focused on developing new therapies for ASMD, including gene therapy.