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Pathway Description
Metachromatic Leukodystrophy (MLD)
Homo sapiens
Disease Pathway
Metachromatic leukodystrophy also known as MLD, is a rare inborn error of metabolism (IEM) which arises from a defective gene called ARSA. The ARSA gene which codes for arylsulfatase. An improperly function arylsulfatase enzyme can lead to the build up of 3-O-sulfogalactosylceramide in urine, neural and non neural tissues like kidney and gallbladder.
MLD like many conditions comes in a slew of different shapes and sizes. The most common these is known as the late infantile form. This form affects children after their first year of age and manifests itself with children having difficulty walking. Of the many other symptoms which present themselves some of them include developmental delays, muscle weakness, rigidity and wasting, convulsions, and dementia, just to name a few. In extreme cases a comatose state may arise in affected children and without treatment, the majority of those affected by late infantile MLD will perish by/or before the age of 5. Another form of MLD is juvenile MLD. Characterized by an age of onset between 3 and 10. It is typically discovered when affected children start to show detiorating school performance, and mental faculties, as well as with the onset of dementia. Progression is slower though very much the same as in the former form of MLD discussed above. Most individuals die 10 to 15 years after the first symptoms manifest. The final form of MLD is adult onset MLD. Defined as occurring after the age of 16 and characterized by progressive dementia or by some psychiatric disorder. The progression of this form is the slowest of the three, and affected individuals may survive a decade or more.
References
Metachromatic Leukodystrophy (MLD) References
[Uniprot: P15289](http://www.uniprot.org/uniprot/P15289)
[OMIM: Entry 250100](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=250100)
Austin J, Armstrong D, Fouch S, Mitchell C, Stumpf D, Shearer L, Briner O: Metachromatic leukodystrophy (MLD). 8. MLD in adults; diagnosis and pathogenesis. Arch Neurol. 1968 Mar;18(3):225-40.
Pubmed: 5642751
Berger J, Gmach M, Mayr U, Molzer B, Bernheimer H: Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity. Hum Mutat. 1999;13(1):61-8. doi: 10.1002/(SICI)1098-1004(1999)13:1<61::AID-HUMU7>3.0.CO;2-H.
Pubmed: 9888390
Biffi A, Cesani M, Fumagalli F, Del Carro U, Baldoli C, Canale S, Gerevini S, Amadio S, Falautano M, Rovelli A, Comi G, Roncarolo MG, Sessa M: Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation. Clin Genet. 2008 Oct;74(4):349-57. doi: 10.1111/j.1399-0004.2008.01058.x. Epub 2008 Sep 11.
Pubmed: 18786133
Bosch EP, Hart MN: Late adult-onset metachromatic leukodystrophy. Dementia and polyneuropathy in a 63-year-old man. Arch Neurol. 1978 Jul;35(7):475-7.
Pubmed: 208495
Gieselmann V, Krageloh-Mann I: Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22.
Pubmed: 20571983
Sphingolipid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
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