Niemann-Pick Disease, Type A

Alternative Names

  • Sphingomyelin Lipidosis
  • Sphingomyelinase Deficiency
  • Niemann-Pick Disease, Intermediate, Protracted Neurovisceral
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number


Mode of Inheritance

Autosomal recessive

Gene Map Locus



Niemann-Pick disease refers to a group of autosomally inherited genetic disorders characterized by abnormalities in lipid metabolism. Of the four known subtypes of Niemann-Pick disease, type A was the first to be discovered. Unfortunately, this type is also the most severe of all forms of the disease. Type A Niemann-Pick disease appears in infancy, and is characterized by abdominal swelling, hepatosplenomegaly, cherry red spot in the eye, feeding difficulties, failure to gain weight and thrive, and a loss of early motor skills which progressively worsens.

Confirmatory diagnosis of suspected cases of Niemann-Pick disease type A can be easily done by measuring the amount of acid sphingomyelinase enzyme in the blood.

Unfortunately, treatment options are limited. Supportive care is the mainstay of management of the condition. Since there is a progressive involvement of the nervous system, most affected children do not survive past 2-3 years of age. Although this is not a very common disease, Ashkenazi Jews show an incidence rate of 1 in 40,000.


Molecular Genetics

Niemann-Pick disease type A is caused due to mutations in the SMPD1 gene, located on chromosome 11p. This gene codes for a lysosomal enzyme called sphingomyelinase, which in its functional state catalyzes the metabolism of lipids, especially sphingomyelin. In individuals with a defect in the SMPD1 gene, the enzymatic activity is severely affected, with most patients showing only 10% of residual activity. This loss of activity leads to an accumulation of sphingomyelin and other such lipids in the cells and tissues of the body, especially the spleen, liver, lungs, and the bone marrow, leading to the pathological features of the condition. Accumulation of the lipids in the central nervous system leads to the neurological sequela noticed.

Studies on the Ashkenazi Jewish population have discovered that more than 90% of patients with the disease have one of three mutations in the SMPD1 gene, L302P, 1bp del fsP330, and R496L.


Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
257200.1LebanonUnknownNo Hepatosplenomegaly; Recurrent acute resp... NM_000543.5:c.1376A>GHomozygousAutosomal, RecessiveJalkh et al. 2019 Parents from the sam...

Other Reports


Louri et al. (2009) described for the first time a case of association of Niemann-Pick disease with syringocystadenoma papilliferum. The patient was a 9-year old boy, in whom a solitary tumor was seen.

Saudi Arabia

Raddadi and Al Twaim (2000) described the case of a 3-year old Saudi boy born to consanguineous parents diagnosed with Neimann-Pick Disease. The patient presented with abdominal distension, weight loss and repeated attacks of chest infections. He had developed a skin rash at 1-year of age, and showed progressive deterioration in attaining his developmental milestones. Upon examination, the child looked sick and emaciated, with a distended abdomen with hepatosplenomegaly, along with lymphadenopathy, muscle wasting, and lack of tone. Papulonodular rashes were present all over the face, neck, trunk, axillae, groin, and buttocks. Both eyes had cherry-red spots. The examination raised the suspicion of Niemann Pick Disease. Laboratory results showed mild hepatic dysfunction, and elevated serum triglyceride levels. Bone marrow aspirate showed foamy vacuolated cells, while the skin nodule was found to have a collection of foamy histocytes and occasional lymphocytes, with small nuclei and vacuolated cytoplasm. The patient was diagnosed with Type A NPD. He did not come for follow-up, and died 3-months later.

Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Among them, 8 cases from 6 families were found to have Neimann-Pick type A, with an estimated incidence of 5 per 100,000 live births. All cases of Neimann-pick were diagnosed by conventional filipin staining and the lack of cholesterol esterification in skin fibroblasts of the patients. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.

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