metachromatic leukodystrophy

      rare inherited metabolic disease in which the lack of a key enzyme causes loss of the protective myelin sheath from the white matter of the brain, resulting in psychological disturbances, mental deterioration, and sensory and motor defects.

      A number of genetic mutations (mutation) have been associated with MLD. Nearly all of these mutations occur in a gene known as ARSA (arylsulfatase A) and result in outright or partial loss of activity of the gene product, an enzyme called arylsulfatase A (ASA), or cerebroside sulfatase. Arylsulfatase A deficiency allows certain harmful sulfur-containing lipids, known as sulfosphingolipids (also called sulfatides), to accumulate in nerve tissues of the central nervous system (nervous system, human) instead of being broken down. Sulfatides can also accumulate in nerve tissue in organs, such as the kidneys (kidney) and gallbladder, where they can cause severe damage.

      There are three types of MLD: infantile (onset occurs within the first four years of life), juvenile (onset occurs between ages 4 and 16), and adult (onset occurs after age 16). The most common form is infantile disease, characterized by a brief period of normal development during the first years of life and then a progressive onset of behavioral problems, mental deterioration, and blindness, ending after several years in death. The juvenile form is characterized by motor disturbances, cognitive deficits, and seizures. Juvenile MLD may be divided into early-juvenile, with onset between ages four and six, and late-juvenile, with onset after age six. The adult disease is characterized mainly by psychological disturbances, including dementia and schizophrenia.

      Specific mutations in ARSA are linked to the timing of MLD onset and the phenotypic (phenotype) patterns (physical manifestations) of MLD, such as the degree of ASA deficiency and the severity of neuropsychiatric symptoms. Other genetic defects, such as those leading to the deficiency of an activator protein involved in the degradation of sulfatides but in which patients have normal ASA levels, can also cause MLD. In addition, there exist individuals who have very low levels of ASA but never develop the disease. This condition is known as pseudoarylsulfatase A deficiency (PASAD) and is the result of two specific polymorphisms (polymorphism) that occur simultaneously in the ARSA gene.

      Treatment options are limited for individuals with MLD. Bone marrow transplantation (transplant) is the only effective treatment, used primarily for stabilizing neurocognitive function, although the disease will often progress despite transplantation. Scientists are investigating gene therapy and stem cell therapy as possible treatment options.

* * *


Universalium. 2010.

Look at other dictionaries:

  • Metachromatic leukodystrophy — Classification and external resources Sulfatide ICD 10 E75.2 …   Wikipedia

  • metachromatic leukodystrophy — n a hereditary neurological disorder of lipid metabolism characterized by the accumulation of cerebroside sulfates, loss of myelin in the central nervous system, and progressive deterioration of mental and motor activity * * * an autosomal… …   Medical dictionary

  • Leukodystrophy — Infobox Disease Name = PAGENAME Caption = DiseasesDB = 32504 ICD10 = ICD10|E|71|3|e|70, ICD10|E|75|2|e|70 ICD9 = ICD9|330.0 ICDO = OMIM = MedlinePlus = eMedicineSubj = eMedicineTopic = MeshID = Leukodystrophy refers to a group of disorders… …   Wikipedia

  • Leukodystrophy — A disorder of the white matter of the brain, the part of the brain that contains myelinated nerve fibers. The white matter is white because it is the color of myelin, the insulation covering the nerve fibers. (The white matter is as opposed to… …   Medical dictionary

  • metachromatic leukoencephalopathy — see under leukodystrophy …   Medical dictionary

  • sulfatide lipidosis — metachromatic leukodystrophy …   Medical dictionary

  • Arylsulfatase A — PDB rendering based on 1auk …   Wikipedia

  • Prosaposin — PDB rendering based on 1m12 …   Wikipedia

  • Psychosis — Not to be confused with Psychopathy. For other uses, see Psychosis (disambiguation). Psychosis Classification and external resources ICD 10 F20 F29[1] ICD 9 …   Wikipedia

  • Leukoencephalopathy with vanishing white matter — Classification and external resources OMIM 603896 Leukoencephalopathy with vanishing white matter (VWM disease) is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the… …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.