Niemann Pick Disease Type A and Type B - causes, symptoms, diagnosis, treatment, pathology

Niemann Pick disease types A and B are two related disorders that are characterized by lysosomal accumulation of sphingomyelin due to an inherited deficiency of sphingomyelinase. Sphingomyelin is a ubiquitous component of cellular and organellar membranes. When cells become old or damaged, they are often phagocytize, or eaten, by macrophages, which are cells of the immune system.
They contain organelles called lysosomes that are said to function as recycling centers because they break down large, potentially harmful substances to be reused by the body.
They break down sphingomyelin by using an enzyme called acid sphingomyelinase, which is a product of the sphingomyelin phosphodiesterase 1, or SMPD1 gene. In Niemann Pick disease types A and B, there’s a mutation in the SMPD1 gene that causes deficiency in the sphingomyelinase enzyme. And so the sphingomyelinase enzyme deficiency blocks degradation of the sphingomyelin, resulting in its progressive accumulation within lysosomes, particularly within cells of the mononuclear phagocyte system. Affected cells become enlarged due to the distention of lysosomes with sphingomyelin.
Innumerable small vacuoles of relatively uniform size are created, imparting foaminess to the cytoplasm. And these cells are called “foam cells.”
Type A is a severe infantile form with extensive neurologic involvement, marked visceral accumulations of sphingomyelin, and progressive wasting and early death within the first 3 years of life. In contrast, type B disease patients have organomegaly but generally no central nervous system involvement. They usually survive into adulthood.
Clinical manifestations in type A disease may be present at birth and almost invariably become evident by age 6 months. Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen by age 3 months and fail to gain weight.
Children with Niemann Pick disease type A also develop widespread lung damage 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.
Now, 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 and does not include neurologic involvement. People with Niemann-Pick disease type B often have recurrent lung infections and splenomegaly which causes a low number of platelets in the blood . They also have short stature and slowed mineralization of bone. People with Niemann-Pick disease type B usually survive into adulthood.
The diagnosis is established by biochemical assays for sphingomyelinase activity in liver or bone marrow biopsy. Individuals affected with types A and B as well as carriers can be detected by DNA analysis.
Treatment of NPC-A includes supportive therapy based on the symptoms that may include a feeding tube and medications to assist with sleeping. NPC-B requires regular lab testing every 6-to-12 months, and appropriate supportive treatment for whichever manifestations develop.

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