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GTR Home > Conditions/Phenotypes > Niemann-Pick disease, type A

Niemann-Pick disease, type A

Synonyms
SPHINGOMYELIN LIPIDOSIS; SPHINGOMYELINASE DEFICIENCY
Modes of inheritance
Autosomal recessive inheritance (Orphanet)

Summary

Excerpted from the GeneReview: Acid Sphingomyelinase Deficiency
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). Enzyme replacement therapy (ERT) is currently FDA approved for the non-central nervous system manifestations of ASMD, regardless of type. As more affected individuals are treated with ERT for longer periods of time, the natural history of ASMD is likely to change. The most common presenting symptom in untreated NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Growth failure typically becomes evident by the second year of life. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. This feature may not be amenable to ERT. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children, although it is unclear if ERT will have an impact on this. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most untreated children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized in untreated individuals by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some central nervous system manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B, even when untreated.
Full text of GeneReview (by section):
Summary
GeneReview Scope
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Melissa P Wasserstein
Edward H Schuchman
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Available tests

139 tests are in the database for this condition.

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Clinical tests (139 available)

Biochemical Genetics Tests

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: ASM, ASMASE, NPD, SMPD1
    Summary: sphingomyelin phosphodiesterase 1

Clinical features

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Imported from Human Phenotype Ontology (HPO)

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Reviews

Clinical resources

Practice guidelines

  • ACMG Algorithm, 2022
    American College of Medical Genetics and Genomics, Algorithm, Acid Sphingomyelinase Deficiency (ASMD): Decreased Acid Sphingomyelinase (ASM), 2022
  • ACMG ACT, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased acid sphingomyelinase, Acid Sphingomyelinase Deficiency (ASMD), 2022
  • ACMG ACT, 2011
    American College of Medical Genetics ACT Sheet, Carrier Screening ACT Sheet Ashkenazi Jewish Genetic Disorders

Molecular resources

Consumer resources

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