Niemann-Pick Disease (NPD) is one of many lysosomal storage diseases that affect metabolism and are caused by genetic mutations. The three most commonly recognized forms of Niemann-Pick Disease are Types A, B and C.
NPA and NPB also known as Acid Sphingomyelinase Deficiency (ASMD) is a lipid storage disorder that results from the deficiency or absence of the lysosomal enzyme acid shpingomyelinase (ASM). This inborn metabolic error is caused by mutations on the SMPD1 gene and is inherited in an autosomal recessive manner. If ASM is absent or not functioning properly, sphingomyelin cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems. Although types A and B are both caused by the same enzymatic deficiency, the clinical prognosis is very different. People with NPA generally have little or no ASM production (less than 1% of normal) while those with NPB have approximately 10% of the normal level of ASM.
There are approximately 1,200 cases of NPA and NPB worldwide with the majority being Type B or an intermediate form.
Niemann-Pick Type A (What Wylder had)
The most severe of all types begins in the first few months of life. Sphingomyelin accumulates in cells called reticuloendothelial cells in the liver and spleen, along with other types of cells throughout the body including the nerve ganglion cells of the central nervous system. Typical cells that have a foamy appearance due to their storage of sphingomyelin are found in the bone marrow, spleen and lymph nodes. The gastrointestinal features include hepatosplenomegaly, jaundice, hepatic (liver) failure, and ascites(fluid in the abdomen). Respiratory problems include pulmonary infiltration, and coronary artery disease occurs early on. A rapid progressive neurodegenerative course that includes seizures, jerks, spasticity, eye paralysis, and ataxia (wobbliness) occurs early on and contribute to the causes of death in early infancy. At some point a cherry-red halo develops around the center of the retina. Children with NPA typically do not live past 2-3 years of age.
Niemann-Pick Type B
In contrast to NPA, patients with NPB generally have little or no neurological involvement and may survive into late childhood or adulthood. Type B individuals usually have enlarged livers and spleens, and respiratory problems are common. The enlargement of organs and the respiratory problems may cause cardiovascular stress and can lead to heart disease later in life. The life expectancy of patients with NPB is highly variable depending on the severity of their symptoms.
Niemann-Pick Type C
NPC is very different than Type A or B (ASMD). NPC Patients are not able to metabolize cholesterol and other lipids properly within the cell. This leads to excessive amounts of cholesterol accumulating within the liver and spleen, and excessive amounts of other lipids accumulate in the brain. NPC causes a secondary reduction of ASM activity, which led all three types to be considered forms of the same disease. Symptoms may appear as early as a few months of age or as late as adulthood, and include vertical gaze palsy, enlarged and/or spleen, and jaundice. In most cases, neurological symptoms begin appearing between the ages of 4 and 10. Generally, the later neurological symptoms begin, the slower the progression of the disease.
Read More at www.NNPDF.org