What is Niemann-Pick Type B?Niemann-Pick is an inherited disease that affects lipid metabolism. It results in harmful amounts of lipids that accumulate in the spleen, brain, lungs, liver, and bone marrow of the affected individual [1]. This accumulation begins in utero, but there are varying ages of onset for Niemann-Pick. People tend to present with symptoms in late childhood or early adulthood [2]. There are four types of Niemann-Pick, and here we will focus specifically on Type B. Common symptoms of type B are growth retardation, hepatosplenomegaly, and lung problems causing frequent lung infections. Hepatosplenomegaly occurs when both the spleen and liver are enlarged simultaneously. People with Niemann-Pick Type B will usually have elevated levels of cholesterol and fats, and a decrease in the number of platelets in their blood. This type does not affect the nervous system, allowing those affected to survive into adulthood. Niemann-Pick Types A and B occur in about 1 out of every 250,000 people. It is an autosomal recessive disease (Figure 2), meaning that an affected child would have parents that are both carriers for the disease [1]. Biopsies of different tissues are commonly evaluated in diagnosing a patient with Niemann-Pick [2]. A less invasive method of diagnosing Niemann-Pick Type B is to evaluate acid sphingomyelinase levels in leukocyte cells from peripheral blood [3].
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Figure 2.This figure represents an autosomal recessive disease inheritance, which is how Niemann-Pick Type B is passed on through generations. If both parents are carriers (such as Paul and Carol), then there is a 25% chance their child will have Niemann-Pick. There is a 50% chance their child will be a carrier, and a 25% chance their child won't be a carrier or have the disease. If only one of the parents is a carrier (such as John and Joan) for Niemann-Pick, then there is no chance of them having a child with Niemann-Pick. There is a 50% chance their child could be a carrier, and a 50% chance they could be unaffected.
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Potential TreatmentsAt this point in time there is no cure or prevention for Niemann-Pick Type B, but within the last 20 years enormous advances in research have occurred. A few therapies that have shown to be effective in mice are bone marrow transplantation, enzyme replacement therapy, and gene therapy [4]. Bone marrow transplants have been found to be effective in some patients with Type B. Enzyme replacement therapy has made advances completing Phase I of clinical trials and should be beginning Phase II in the near future [3]. Gene therapy testing is just beginning in mice, but shows the most promise. In gene therapy, the defective gene is replaced with a healthy gene thereby allowing for normal lipid metabolism. The video on the right explains the process of gene therapy. Physical therapy and supportive care are crucial in helping improve the patient's quality of life, and specialists can help with muscle tone, eating problems, and seizures [4].
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Role of SMPD1 in Niemann Pick Disease
The sphingomyelin phosphodiesterase 1 (SMPD1) gene encodes for acid sphingomyelinase, which is an enzyme found in lysozomes. The enzyme functions to break down lipids. Mutations in the SMPD1 gene prevent it from breaking down lipids, which causes Niemann-Pick Type B disease. Cholesterol, sphingomyelin, and other types of lipids start to accumulate in the affected individual leading to enlarged spleens and livers [1]. The accumulation of sphingomyelin occurs most often in monocyte and macrophage cell lineages [2]. To learn more about the SMPD1 gene, make sure to visit the Gene page!
References
[Header Figure] from WebPathology. (2013). Niemann-Pick Disease Spleen [Photograph]. Retrieved from http://www.webpathology.com/image.asp?case=377&n=6 Copyright 2011 by WebPathology.com.
[Figure 1] from Medindia. Retrieved from http://www.medindia.net/patients/patientinfo/niemann-pick-disease.htm
[Figure 2] from Niemann-Pick Disease Group, United Kingdom. (2010). Liver cell biopsy [Photograph]. Retrieved from http://www.niemannpick.org.uk/what_is_npd/faq.html Copyright 2010 by Niemann-Pick Disease Group (UK).
[Video] from Cortical Studios, Amsterdam. (2009). Gene Therapy [Video]. Retrieved from http://www.youtube.com/watch?v=imL1Zmi3mWk Copyright 2009 by Corical Studios (Amsterdam).
[1] http://ghr.nlm.nih.gov/condition/niemann-pick-disease
[2] Thurberg, B. L., Wasserstein, M. P., Schiano, T., O’Brien, F., Richards, S., Cox, G., & McGovern, M. M. (2012). Liver and Skin Histopathology in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B). The American Journal of Surgical Pathology, 36(8), 1234. doi: 10.1097/PAS.0b013e31825793ff
[3] Zhang, H., Wang, Y., Gong, Z., Li, X., Qiu, W., Han, L., Ye, J. (2013). Identification of a distinct mutation spectrum in the SMPD1 gene of Chinese patients with acid sphingomyelinase-deficient Niemann-Pick disease. Orphanet Journel of Rare Diseases, 8(15). doi: 10.1186/1750-1172-8-15
[4] http://www.mayoclinic.org/niemann-pick/treatment.html
[Header Figure] from WebPathology. (2013). Niemann-Pick Disease Spleen [Photograph]. Retrieved from http://www.webpathology.com/image.asp?case=377&n=6 Copyright 2011 by WebPathology.com.
[Figure 1] from Medindia. Retrieved from http://www.medindia.net/patients/patientinfo/niemann-pick-disease.htm
[Figure 2] from Niemann-Pick Disease Group, United Kingdom. (2010). Liver cell biopsy [Photograph]. Retrieved from http://www.niemannpick.org.uk/what_is_npd/faq.html Copyright 2010 by Niemann-Pick Disease Group (UK).
[Video] from Cortical Studios, Amsterdam. (2009). Gene Therapy [Video]. Retrieved from http://www.youtube.com/watch?v=imL1Zmi3mWk Copyright 2009 by Corical Studios (Amsterdam).
[1] http://ghr.nlm.nih.gov/condition/niemann-pick-disease
[2] Thurberg, B. L., Wasserstein, M. P., Schiano, T., O’Brien, F., Richards, S., Cox, G., & McGovern, M. M. (2012). Liver and Skin Histopathology in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B). The American Journal of Surgical Pathology, 36(8), 1234. doi: 10.1097/PAS.0b013e31825793ff
[3] Zhang, H., Wang, Y., Gong, Z., Li, X., Qiu, W., Han, L., Ye, J. (2013). Identification of a distinct mutation spectrum in the SMPD1 gene of Chinese patients with acid sphingomyelinase-deficient Niemann-Pick disease. Orphanet Journel of Rare Diseases, 8(15). doi: 10.1186/1750-1172-8-15
[4] http://www.mayoclinic.org/niemann-pick/treatment.html