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Metachromatic leukodystrophy
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Metachromatic leukodystrophy
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the growth and/or development of myelin, the fatty covering that acts as an insulator around nerve fibers throughout the central and peripheral nervous systems. MLD involves cerebroside sulfate accumulation. Metachromatic leukodystrophy, like most enzyme deficiencies, has an autosomal recessive inheritance pattern.
Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult.[citation needed]
Palliative care can help with many of the symptoms and usually improves the quality of life and longevity.[citation needed]
Carriers have low enzyme levels compared to their family population ("normal" levels vary from family to family) but even low enzyme levels are adequate to process the body's sulfatide.[citation needed]
MLD is directly caused by a deficiency of the enzyme arylsulfatase A (ARSA) and is characterized by enzyme activity in leukocytes that is less than 10% of normal controls. However, assay of the ARSA enzyme activity alone is not sufficient for diagnosis; ARSA pseudodeficiency, which is characterized by enzyme activity that is 5~20% of normal controls does not cause MLD. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system. The myelin sheath is a fatty covering that protects nerve fibers. Without it, the nerves in the brain (central nervous system – CNS) and the peripheral nerves (peripheral nervous system – PNS) which control, among other things the muscles related to mobility, cease to function properly.[citation needed]
Arylsulfatase A is activated by saposin B (Sap B), a non-enzymatic proteinaceous cofactor. When the arylsulfatase A enzyme level is normal but the sulfatides are still high – meaning that they are not being broken down because the enzyme is not activated – the resulting disease is saposin B deficiency, which presents similar to MLD. Saposin B deficiency is very rare, much more rare than traditional MLD. The enzyme that is present is not "enabled" to a normal level of efficiency and can't break down the sulfatides which results in all of the same MLD symptoms and progression.
A 2011 study contended sulfatide is not completely responsible for MLD because it is non-toxic. It has been suggested that lysosulfatide, sulfatide which has had its acyl group removed, plays a role because of its cytotoxic properties in vitro.
MLD has an autosomal recessive inheritance pattern. The inheritance probabilities per birth are as follows:
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Metachromatic leukodystrophy
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the growth and/or development of myelin, the fatty covering that acts as an insulator around nerve fibers throughout the central and peripheral nervous systems. MLD involves cerebroside sulfate accumulation. Metachromatic leukodystrophy, like most enzyme deficiencies, has an autosomal recessive inheritance pattern.
Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult.[citation needed]
Palliative care can help with many of the symptoms and usually improves the quality of life and longevity.[citation needed]
Carriers have low enzyme levels compared to their family population ("normal" levels vary from family to family) but even low enzyme levels are adequate to process the body's sulfatide.[citation needed]
MLD is directly caused by a deficiency of the enzyme arylsulfatase A (ARSA) and is characterized by enzyme activity in leukocytes that is less than 10% of normal controls. However, assay of the ARSA enzyme activity alone is not sufficient for diagnosis; ARSA pseudodeficiency, which is characterized by enzyme activity that is 5~20% of normal controls does not cause MLD. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system. The myelin sheath is a fatty covering that protects nerve fibers. Without it, the nerves in the brain (central nervous system – CNS) and the peripheral nerves (peripheral nervous system – PNS) which control, among other things the muscles related to mobility, cease to function properly.[citation needed]
Arylsulfatase A is activated by saposin B (Sap B), a non-enzymatic proteinaceous cofactor. When the arylsulfatase A enzyme level is normal but the sulfatides are still high – meaning that they are not being broken down because the enzyme is not activated – the resulting disease is saposin B deficiency, which presents similar to MLD. Saposin B deficiency is very rare, much more rare than traditional MLD. The enzyme that is present is not "enabled" to a normal level of efficiency and can't break down the sulfatides which results in all of the same MLD symptoms and progression.
A 2011 study contended sulfatide is not completely responsible for MLD because it is non-toxic. It has been suggested that lysosulfatide, sulfatide which has had its acyl group removed, plays a role because of its cytotoxic properties in vitro.
MLD has an autosomal recessive inheritance pattern. The inheritance probabilities per birth are as follows: