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Pathway Description
Metachromatic Leukodystrophy (MLD)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
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
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
Imamura T, Ohgane J, Ito S, Ogawa T, Hattori N, Tanaka S, Shiota K: CpG island of rat sphingosine kinase-1 gene: tissue-dependent DNA methylation status and multiple alternative first exons. Genomics. 2001 Aug;76(1-3):117-25. doi: 10.1006/geno.2001.6607.
Pubmed: 11560121
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Pubmed: 15489334
Maceyka M, Sankala H, Hait NC, Le Stunff H, Liu H, Toman R, Collier C, Zhang M, Satin LS, Merrill AH Jr, Milstien S, Spiegel S: SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. J Biol Chem. 2005 Nov 4;280(44):37118-29. doi: 10.1074/jbc.M502207200. Epub 2005 Aug 23.
Pubmed: 16118219
Jasinska R, Zhang QX, Pilquil C, Singh I, Xu J, Dewald J, Dillon DA, Berthiaume LG, Carman GM, Waggoner DW, Brindley DN: Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters. Biochem J. 1999 Jun 15;340 ( Pt 3):677-86.
Pubmed: 10359651
Nanjundan M, Possmayer F: Molecular cloning and expression of pulmonary lipid phosphate phosphohydrolases. Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1484-93. doi: 10.1152/ajplung.2001.281.6.L1484.
Pubmed: 11704545
Waggoner DW, Gomez-Munoz A, Dewald J, Brindley DN: Phosphatidate phosphohydrolase catalyzes the hydrolysis of ceramide 1-phosphate, lysophosphatidate, and sphingosine 1-phosphate. J Biol Chem. 1996 Jul 12;271(28):16506-9. doi: 10.1074/jbc.271.28.16506.
Pubmed: 8663293
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000347
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