Niemann-Pick disease, SMPD1-associated
Encyclopedia
Niemann-Pick disease, SMPD1-associated refers to two different types of Niemann-Pick disease
which are associated with the SMPD1 gene.
There are approximately 1,200 cases of NPA and NPB worldwide with the majority of cases being Type B or an intermediate form.
Descriptions of type E and type F have been published, but they are not well characterized, and are currently classified under type B.
, an enlarged liver, failure to thrive
, progressive deterioration of the nervous system
and profound brain damage. Children affected by Niemann Pick Type A rarely live beyond 18 months. Niemann-Pick Type A occurs more frequently among individuals of Ashkenazi
(eastern and central European) Jewish descent than in other ethnicities. The incidence within the Ashkenazi population is approximately 1 in 40,000 people. The incidence for other populations is unknown.
, growth retardation, and problems with lung function including frequent lung
infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cell
s involved in clotting (platelets). The brain is not affected in Type B and the disease often presents in the pre-teen years.
called acid sphingomyelinase. Insufficient activity of the enzyme acid sphingomyelinase causes the build up of toxic amounts of sphingomyelin
, a fatty substance present in every cell
of the body. This enzyme is found in special compartments within cells called lysosomes (compartments that digest and recycle materials in the cell), and is required to metabolize the lipid
sphingomyelin. If sphingomyelinase 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.
Niemann-Pick disease
Niemann–Pick disease refers to a group of fatal inherited metabolic disorders that are included in the larger family of lysosomal storage diseases .-Signs and symptoms:Symptoms are related to the organs in which they accumulate...
which are associated with the SMPD1 gene.
There are approximately 1,200 cases of NPA and NPB worldwide with the majority of cases being Type B or an intermediate form.
Descriptions of type E and type F have been published, but they are not well characterized, and are currently classified under type B.
Type A
Niemann-Pick Type A, the most common type, occurs in infants and is characterized by jaundiceJaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, an enlarged liver, failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
, progressive deterioration of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and profound brain damage. Children affected by Niemann Pick Type A rarely live beyond 18 months. Niemann-Pick Type A occurs more frequently among individuals of Ashkenazi
Ashkenazi Jews
Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim , are the Jews descended from the medieval Jewish communities along the Rhine in Germany from Alsace in the south to the Rhineland in the north. Ashkenaz is the medieval Hebrew name for this region and thus for Germany...
(eastern and central European) Jewish descent than in other ethnicities. The incidence within the Ashkenazi population is approximately 1 in 40,000 people. The incidence for other populations is unknown.
Type B
Niemann-Pick Type B involves an enlarged liver and spleen hepatosplenomegalyHepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
, growth retardation, and problems with lung function including frequent lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cell
Blood cell
A blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...
s involved in clotting (platelets). The brain is not affected in Type B and the disease often presents in the pre-teen years.
Genetics
Mutations in the SMPD1 gene cause Niemann-Pick Types A and B. This gene carries instructions for cells to produce an enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
called acid sphingomyelinase. Insufficient activity of the enzyme acid sphingomyelinase causes the build up of toxic amounts of sphingomyelin
Sphingomyelin
Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphorylcholine and ceramide...
, a fatty substance present in every cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
of the body. This enzyme is found in special compartments within cells called lysosomes (compartments that digest and recycle materials in the cell), and is required to metabolize the lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
sphingomyelin. If sphingomyelinase 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.