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not medical advice.
Everything here is tied to published research. If something you expected is not here, it almost always means we have not mapped a source for it yet,
not that it is unknown to medicine.
acid sphingomyelinase deficiency is an early, growing map, so it will look incomplete on purpose: we would rather show less and have every line be something you can check than fill the page with claims we cannot stand behind.
For anything about your own situation, your clinicians hold the full picture.
How this guide is built and why.
What's acid sphingomyelinase deficiency?
Acid sphingomyelinase deficiency (ASMD), historically called Niemann-Pick disease types A and B, is a rare autosomal recessive lysosomal storage disorder caused by variants in SMPD1, the gene for the enzyme acid sphingomyelinase. Without the enzyme, sphingomyelin accumulates in cells. It runs along a spectrum: type A is the severe infantile neuronopathic form (rapid neurodegeneration, cherry-red macula, early death); type B is a chronic, largely non-neuronopathic visceral form (hepatosplenomegaly, interstitial lung disease, survival into adulthood); intermediate (type A/B) forms also occur. This is a distinct entity from Niemann-Pick type C, which is a cholesterol-trafficking defect (NPC1/NPC2), not an enzyme deficiency.
| Also indexed as | OMIM:257200, MONDO:0009756 |
|---|
| Features mapped | 9 |
|---|
| Treatments mapped | 3 |
|---|
| Published sources | 11 |
|---|
| Last reviewed | 2026-08-04 |
|---|
Signs and symptoms
Global developmental delay
In the neuronopathic (type A and intermediate A/B) forms, the brain is affected and children show developmental delay and, later, regression.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:35534800
Notesplain_language confirmed from PMID:35534800 via curation 2026-06-14.
Last reviewed2026-06-14
Splenomegaly
An enlarged spleen is one of the hallmark features of acid sphingomyelinase deficiency type B, which often also enlarges the liver.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:35534800, PMID:41879707, OMIM:607616
Notesplain_language confirmed from PMID:35534800 via curation 2026-06-14. plain_language confirmed from PMID:41879707 via curation 2026-06-25 [claude-draft]. | regrounded primary OMIM:607616 -> PMID:30795770 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Failure to thrive
Poor growth and failure to thrive are common in the more severe forms, reflecting the systemic burden of the disease in infancy and early childhood.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41208004, OMIM:257200
Notesplain_language confirmed from PMID:41208004 via curation 2026-06-14. | regrounded primary OMIM:257200 -> PMID:28228103 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Autosomal recessive inheritance
Acid sphingomyelinase deficiency is inherited in an autosomal recessive way, meaning a person develops it only when they inherit a changed SMPD1 gene from each parent.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41791926, PMID:41208004, OMIM:607616
Notesplain_language confirmed from PMID:41791926 via curation 2026-06-17. plain_language confirmed from PMID:41208004 via curation 2026-06-25 [claude-draft]. | regrounded primary OMIM:607616 -> PMID:28228103 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Sea-blue histiocytosis
Lipid-laden storage cells, including foamy Niemann-Pick cells and sea-blue histiocytes, are found in the bone marrow and help point to the diagnosis.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41791926
Notesplain_language confirmed from PMID:41791926 via curation 2026-06-14.
Last reviewed2026-06-14
Recurrent respiratory infections
Lung involvement is common, especially in type B, with interstitial lung disease and recurrent respiratory infections that can progress to respiratory difficulty.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesOMIM:607616
Notesplain_language confirmed from PMID:38397448 via curation 2026-06-14. | regrounded primary OMIM:607616 -> PMID:38397448 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Cherry red spot of the macula
A cherry-red spot at the macula of the eye is a characteristic finding, prominent in the severe infantile (type A) form and also seen in some type B patients.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41208004, OMIM:257200
Notesplain_language confirmed from PMID:41208004 via curation 2026-06-14. | regrounded primary OMIM:257200 -> PMID:30795770 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Hepatomegaly
An enlarged liver, usually together with an enlarged spleen, is a characteristic feature of acid sphingomyelinase deficiency type B.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41879707, OMIM:607616
Notesplain_language confirmed from PMID:41879707 via curation 2026-06-25 [claude-draft]. | regrounded primary OMIM:607616 -> PMID:30795770 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
Decreased acid sphingomyelinase activity
Acid sphingomyelinase deficiency comes from a lack of acid sphingomyelinase activity, caused by changes in the SMPD1 gene. Measuring this low enzyme activity is central to recognizing the condition.
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41208004, OMIM:607616
Notesplain_language confirmed from PMID:41208004 via curation 2026-06-14. plain_language confirmed from PMID:38397448 via curation 2026-06-25 [claude-draft]. | regrounded primary OMIM:607616 -> PMID:38397448 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26
How it is diagnosed
Niemann-Pick disease, type A
Diagnosed using: Biopsy.
The source text this rests on
“Transjugular liver biopsy demonstrated foamy cells infiltration, while bone marrow examination identified sea-blue histiocytes (approximately 4.5% of nucleated cells) and Niemann-Pick cells (approximately 2.5%).”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41791926 via curation 2026-06-17
Last reviewed2026-06-17
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
olipudase alfa
Olipudase alfa is enzyme replacement therapy: a manufactured copy of acid sphingomyelinase given by infusion. It is the first disease-specific treatment for ASMD and improves the non-neurological manifestations (spleen and liver size, lung function, lipid profile). Because it does not cross into the brain, it does not treat the central-nervous-system disease of the severe type A form.
Used to help with: Niemann-Pick disease, type A.
The source text this rests on
“Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:35639287
Notesconfirmed from PMID:37098529 via curation 2026-06-14 | superseded (replace) by PMID:35639287 on 2026-06-19 [carrie]
Last reviewed2026-06-19
hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation and, for advanced lung disease, lung transplantation have been described for ASMD in selected cases, though experience is limited and they are not standard disease-modifying therapy.
Used to help with: Niemann-Pick disease, type A.
The source text this rests on
“…hematopoietic stem cell transplantation are also described for…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:38397448 via curation 2026-06-14
Last reviewed2026-06-14
Enzyme replacement therapy
Enzyme replacement therapy with olipudase alfa is the first and currently only disease-modifying treatment for the non-nervous-system effects of acid sphingomyelinase deficiency. In studies it has improved the enlarged liver and spleen, lung function, and platelet counts.
Used to help with: Niemann-Pick disease, type A.
The source text this rests on
“BACKGROUND: Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:37133675
Notesconfirmed from PMID:37098529 via curation 2026-06-17 | superseded (replace) by PMID:37133675 on 2026-06-19 [carrie]
Last reviewed2026-06-19
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
SMPD1 enzyme deficiency
Acid sphingomyelinase deficiency is caused by changes in the SMPD1 gene, which carries the instructions for the enzyme acid sphingomyelinase. When this enzyme is missing or does not work, the body cannot break down a fat called sphingomyelin, so it builds up inside cells.
Described as modulating: Niemann-Pick disease, type A.
The source text this rests on
“NPD type A and B are caused by mutations in the gene SMPD1 coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:38397448 via curation 2026-06-25
Last reviewed2026-06-25
type A vs type B severity spectrum
Acid sphingomyelinase deficiency spans a wide range of severity. Type A causes severe nervous-system damage in infancy, while type B is a milder form that mainly affects the organs; type A/B falls in between.
Described as modulating: Niemann-Pick disease, type A.
The source text this rests on
“It is characterized by sphingomyelin accumulation and a broad clinical spectrum ranging from severe neurodegeneration in type A to a milder visceral phenotype in type…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41208004 via curation 2026-06-25
Last reviewed2026-06-25
How to read the evidence labels
Widely acceptedSpecialists broadly agree on this.
Strong evidenceBacked by solid, repeated research.
Moderate evidenceReasonable evidence, still being confirmed.
Limited evidenceSome evidence, but not yet convincing.
Early evidenceAn early finding that needs more study.
Experts disagreeResearchers actively disagree about this.
No longer supportedLater, stronger evidence or guidance overturned this.
Where this comes from
This guide is built from 11 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
OMIM:257200 · Orphanet/HPO annotations for Niemann-Pick disease, type A
OMIM:607616 · Orphanet/HPO annotations for Niemann-pick disease, type B
PMID:28228103 · Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD).
PMID:30795770 · Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up.
PMID:37098529 · Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinica
PMID:37133675 · Olipudase Alfa in Non-CNS Manifestations of Acid Sphingomyelinase Deficiency: A Profile of Its Use.
PMID:38397448 · The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review.
PMID:41208004 · Exploring the boundaries of Niemann-Pick disease type A/B: a report of a case and review of literature.
PMID:41692468 · Pathogenic Variants and Olipudase Alfa Treatment of Patients With Acid Sphingomyelinase Deficiency in Taiwan.
PMID:41791926 · Suspected Niemann-Pick disease type B with sea-blue histiocytosis after splenectomy: A rare case report.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.