Sphingomyelinase Deficiency Workup

Updated: Aug 18, 2016
  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Approach Considerations

CBC count

Pancytopenia may be present secondary to the enlarged spleen in patients with Niemann-Pick disease (NPD).

Serum chemistry

Transaminase levels may be elevated.


Reduced high-density lipoprotein (HDL-C) fraction is common in NPD type B. In most patients, this is accompanied by elevated total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels.


Most patients with NPD type B and low serum HDL-C levels also have hypertriglyceridemia.

Chest radiography Chest radiography reveals a typical reticulonodular pattern of infiltration, even in patients with no overt pulmonary symptoms. Calcified pulmonary nodules may be seen.

Bone age in patients with NPD type B can lag as long as 2.5 years behind the chronologic age.

Pulmonary function testing

Testing typically reveals decreased oxygen diffusion, restrictive lung disease, and decreased maximal exercise tolerance.

Echocardiogram (ECHO)

ECHO may reveal valve dysfunction in patients with valvular heart disease and myocardial dysfunction in those with underlying coronary artery disease.

Electrocardiography (ECG) and stress testing

Testing may be abnormal in patients with hyperlipidemia and evidence of coronary artery disease.


Acid Sphingomyelinase


The diagnosis of Niemann-Pick disease (NPD) is confirmed with measurement of enzyme activity in peripheral white blood cells or in cultured fibroblasts.

Mutation analysis

Targeted mutation analysis for 4 common SMPD1 mutations is available in clinical laboratories. Three common type A mutations (L302P, R496L, fsP330) predict the severe infantile form of the disease common in the Ashkenazi Jewish population. One common type B allele (deltaR608) is associated with the non-neuronopathic, milder form of disease. Individuals with the Gln294Lys mutation, often associated with NPD type B with progressive neurologic findings, may have apparently normal enzymatic activity when artificial substrate is used. [10] Sequence and deletion/duplication analysis of the gene is available in clinical laboratories and permits identification of rare and private gene mutations. This information is useful for genotype-phenotype correlation. In addition, genotype information allows identification of carriers among at-risk family members and allows prenatal diagnosis using fetal DNA analysis.


Histologic Findings

The pathologic hallmark in Niemann-Pick disease (NPD) types A and B is the histochemically characteristic lipid-laden foam cell, often termed the Niemann-Pick cell, on bone marrow examination.

These cells, which can be readily distinguished from Gaucher cells by histologic and histochemical characteristics, are not pathognomic for NPD. Histologically similar lipid-laden foam cells are found in patients with Wolman disease, cholesterol ester storage disease, lipoprotein lipase deficiency, NPD type C, and, in some patients, GM1 gangliosidosis type 2.

Bone marrow examination is not necessary for the diagnosis of NPD.