Acid Sphingomyelinase Deficiency (Niemann-Pick Disease), Types A and B
Acid sphingomyelinase breaks down a lipid called sphingomyelin. With both types A and B, the enzyme is deficient, with the more severe deficiency associated with the A phenotype. Sphingomyelin and cholesterol accumulate in lysosomes to form fatty deposits with a foamy, swollen appearance. Acid sphingomyelinase (ASM) deficiency is distinguished clinically from Niemann-Pick type C (which results from cholesterol transport defects) by the following:  Absence of vertical supranuclear ophthalmoplegia in type C Early and rapid neurological decline in neuronopathic ASM deficiency Apparent lack of progression or total absence of neurologic symptoms in non-neuronopathic ASM deficiency Key Symptom Images Image Credits: Hepatosplenomegaly courtesy of The National MPS Society, Inc.
Clinical Description [3,4]Patients with acid sphingomyelinase (ASM) deficiency show evidence of fatty deposits in one or more organs. Those with neuronopathic ASM deficiency generally present within the first few months and were historically classified as having Niemann-Pick disease type A. Patients with non-neuronopathic ASM deficiency can present at any age and were historically classified as having Niemann-Pick disease type B. However, these clinical descriptions represent the extremes of a heterogeneous disease continuum and should not be used to predict disease course.
In patients with partial enzyme deficiencies, the accumulation of sphingomyelin and Niemann-Pick cells leads to hepatosplenomegaly, pulmonary infiltration and insufficiency, significant growth and pubertal delay, and elevated tissue cholesterol levels. The age and cause of death are variable. More severe enzyme deficiencies also lead to clinically significant accumulation of sphingomyelin in the brain with progressive neurological impairment and death, usually by age 3. Inheritance pattern: autosomal recessive Incidence: pan-ethnic, type A higher frequency among Ashkenazi Jews [5]; 1 in 248,000 live births [5] Diagnosis: enzyme assay Conditions with similar presentations: Gaucher disease; GM1 Gangliodosis Management: no disease-specific treatment available; clinical trials for enzyme replacement therapy under investigation Other medical care:[2] symptom management
Mental retardation Spasticity Seizures Myoclonic jerks Vertical supranuclear ophthalmoplegia Ataxia Hepatosplenomegaly Jaundice Hepatic failure Ascites Recurrent vomiting Chronic constipation General
Retarded physical growth
Ocular Cherry-red macular spots Corneal opacities Brown discoloration of the anterior lens capsule Back to categories Nodular xanthoma Hematologic Bone marrow foam cells Easy bruising Anemia Pancytopenia Respiratory Interstitial pulmonary infiltration Cardiovascular Coronary artery disease Back to categories
1. Nyhan W, Pinar O. Atlas of Metabolic Diseases. London: Chapman & Hall;1998 London. Pp. 566-574.
2. National Niemann-Pick Disease Foundation, Inc. www.nnpdf.org. Accessed July 2004.
3. Medicinenet. www.medicinenet.com/script/main/Art.asp?Li=MNI&articlekey=10153 Accessed July 2004.
4. National Tay-Sachs & Allied Diseases Association. www.ntsad.org/pages/n-pick.htm Accessed July 2004.
5 Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254.
7. National Institute of Neurological Disorders and Stroke. www.ninds.nih.gov/health_and_medical/disorders/niemann.doc.htm Accessed July 2004.
8. National Center for Biotechnology Information; OMIM(TM), Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?257200.cs Accessed July 2004.
9. National Niemann-Pick Disease Foundation, Inc. www.nnpdf.org/symptoms.htm Accessed July 2004. |
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