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Sphingomyelin/cholesterol lipidosis

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: Niemann-Pick disease
SNOMED CT: Sphingomyelin/cholesterol lipidosis (58459009); Neuronal cholesterol lipidosis (58459009); Sphingomyelinase deficiency (58459009); Niemann-Pick disease (58459009); Sphingomyelin lipidosis (58459009)
Related genes: NPC2, SMPD1, NPC1
Monarch Initiative: MONDO:0001982

Disease characteristics

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. [from GeneReviews]
Melissa P Wasserstein  |  Edward H Schuchman   view full author information

Additional description

From MedlinePlus Genetics
Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.

Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.

The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.  https://medlineplus.gov/genetics/condition/niemann-pick-disease

Professional guidelines


Geberhiwot T, Wasserstein M, Wanninayake S, Bolton SC, Dardis A, Lehman A, Lidove O, Dawson C, Giugliani R, Imrie J, Hopkin J, Green J, de Vicente Corbeira D, Madathil S, Mengel E, Ezgü F, Pettazzoni M, Sjouke B, Hollak C, Vanier MT, McGovern M, Schuchman E
Orphanet J Rare Dis 2023 Apr 17;18(1):85. doi: 10.1186/s13023-023-02686-6. PMID: 37069638Free PMC Article
Hu J, Maegawa GHB, Zhan X, Gao X, Wang Y, Xu F, Qiu W, Han L, Gu X, Zhang H
Hum Mutat 2021 May;42(5):614-625. Epub 2021 Mar 19 doi: 10.1002/humu.24192. PMID: 33675270
McGovern MM, Dionisi-Vici C, Giugliani R, Hwu P, Lidove O, Lukacs Z, Eugen Mengel K, Mistry PK, Schuchman EH, Wasserstein MP
Genet Med 2017 Sep;19(9):967-974. Epub 2017 Apr 13 doi: 10.1038/gim.2017.7. PMID: 28406489Free PMC Article


American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased acid sphingomyelinase, Acid Sphingomyelinase Deficiency (ASMD), 2022

American College of Medical Genetics and Genomics, Algorithm, Acid Sphingomyelinase Deficiency (ASMD): Decreased Acid Sphingomyelinase (ASM), 2022

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.


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

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