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Pathway Description
Gaucher Disease
Homo sapiens
Disease Pathway
Created: 2022-11-22
Last Updated: 2023-10-25
Gaucher disease, also known as glucocerebrosidase deficiency, acid beta-glucosidase deficiency or GBA deficiency, refers to a group of autosomal recessively inherited rare inborn error of metabolism (IEM) that affect the sphingolipid metabolism pathway. All forms of Gaucher disease is caused by a mutation in the GBA gene that encodes lysosomal acid glucosylceramidase, an enzyme that is responsible for catalyzing the formation of ceramide and glucose from glucosylceramide via a hydrolysis reaction. Gaucher disease is characterized by the intracellular buildup of glucosylceramides, particularly in phagocytes, forming what are known as Gaucher cells. Symptoms include anemia, fatigue, hepatomegaly and splenomegaly, however these may vary based on the type of Gaucher disease. For example, type 1 (GD1) involves hepato- and splenomegaly, and types 2 and 3 (GD2 and GD3) also typically affect the brain and spinal cord, and as such tend to be more severe and more likely to become lethal. Treatment for Gaucher disease includes enzyme replacement therapy for type 1, which also helps treat types 2 and 3, but as the enzymes cannot cross the blood-brain barrier, cannot help with the brain damage associated with these types. A drug called miglustat, sold as Zavesca, can also be used to treat the symptoms of type 1 Gaucher disease in individuals who cannot have enzyme replacement therapy. It is estimated that Gaucher disease affects 1 in 100,000 individuals, with the rates being higher in certain populations such as Ashkenazi Jews. GD1 is the most common in most populations representing around 90% of cases of Gaucher disease, with GD2 and GD3 representing roughly 5% each.
References
Gaucher Disease References
Blom S, Erikson A: Gaucher disease--Norrbottnian type. Neurodevelopmental, neurological, and neurophysiological aspects. Eur J Pediatr. 1983 Sep;140(4):316-22. doi: 10.1007/BF00442672.
Pubmed: 6628452
Dahl N, Hillborg PO, Olofsson A: Gaucher disease (Norrbottnian type III): probable founders identified by genealogical and molecular studies. Hum Genet. 1993 Nov;92(5):513-5. doi: 10.1007/BF00216461.
Pubmed: 8244344
Dahl N, Lagerstrom M, Erikson A, Pettersson U: Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene. Am J Hum Genet. 1990 Aug;47(2):275-8.
Pubmed: 2378352
Pastores GM, Hughes DA: Gaucher Disease.
Pubmed: 20301446
Farfel-Becker T, Vitner EB, Futerman AH: Animal models for Gaucher disease research. Dis Model Mech. 2011 Nov;4(6):746-52. doi: 10.1242/dmm.008185. Epub 2011 Oct 4.
Pubmed: 21954067
Gozdasoglu S: Gaucher Disease and Gaucher Cells. Turk J Haematol. 2015 Jun;32(2):187-8. doi: 10.4274/tjh.2015.0043.
Pubmed: 26316492
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.
Rotthier A, Auer-Grumbach M, Janssens K, Baets J, Penno A, Almeida-Souza L, Van Hoof K, Jacobs A, De Vriendt E, Schlotter-Weigel B, Loscher W, Vondracek P, Seeman P, De Jonghe P, Van Dijck P, Jordanova A, Hornemann T, Timmerman V: Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am J Hum Genet. 2010 Oct 8;87(4):513-22. doi: 10.1016/j.ajhg.2010.09.010.
Pubmed: 20920666
Weiss B, Stoffel W: Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis. Eur J Biochem. 1997 Oct 1;249(1):239-47. doi: 10.1111/j.1432-1033.1997.00239.x.
Pubmed: 9363775
Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Feb 28;5(1):31-9. doi: 10.1093/dnares/5.1.31.
Pubmed: 9628581
Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA: Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. 2001 Mar;27(3):309-12. doi: 10.1038/85879.
Pubmed: 11242114
Taouji S, Higa A, Delom F, Palcy S, Mahon FX, Pasquet JM, Bosse R, Segui B, Chevet E: Phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 inhibits its activity and promotes cell survival. J Biol Chem. 2013 Jun 14;288(24):17190-201. doi: 10.1074/jbc.M112.409185. Epub 2013 Apr 29.
Pubmed: 23629659
Verhoeven K, Coen K, De Vriendt E, Jacobs A, Van Gerwen V, Smouts I, Pou-Serradell A, Martin JJ, Timmerman V, De Jonghe P: SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology. 2004 Mar 23;62(6):1001-2. doi: 10.1212/01.wnl.0000115388.10828.5c.
Pubmed: 15037712
Rimokh R, Gadoux M, Bertheas MF, Berger F, Garoscio M, Deleage G, Germain D, Magaud JP: FVT-1, a novel human transcription unit affected by variant translocation t(2;18)(p11;q21) of follicular lymphoma. Blood. 1993 Jan 1;81(1):136-42.
Pubmed: 8417785
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. doi: 10.1038/nature03983.
Pubmed: 16177791
Igarashi N, Okada T, Hayashi S, Fujita T, Jahangeer S, Nakamura S: Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. J Biol Chem. 2003 Nov 21;278(47):46832-9. doi: 10.1074/jbc.M306577200. Epub 2003 Sep 2.
Pubmed: 12954646
Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S: Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000 Jun 30;275(26):19513-20. doi: 10.1074/jbc.M002759200.
Pubmed: 10751414
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. doi: 10.1101/gr.gr1547r.
Pubmed: 11230166
Ogawa C, Kihara A, Gokoh M, Igarashi Y: Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J Biol Chem. 2003 Jan 10;278(2):1268-72. doi: 10.1074/jbc.M209514200. Epub 2002 Oct 30.
Pubmed: 12411432
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Kai M, Wada I, Imai Si, Sakane F, Kanoh H: Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase. J Biol Chem. 1997 Sep 26;272(39):24572-8. doi: 10.1074/jbc.272.39.24572.
Pubmed: 9305923
Leung DW, Tompkins CK, White T: Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells. DNA Cell Biol. 1998 Apr;17(4):377-85. doi: 10.1089/dna.1998.17.377.
Pubmed: 9570154
Ulrix W, Swinnen JV, Heyns W, Verhoeven G: Identification of the phosphatidic acid phosphatase type 2a isozyme as an androgen-regulated gene in the human prostatic adenocarcinoma cell line LNCaP. J Biol Chem. 1998 Feb 20;273(8):4660-5. doi: 10.1074/jbc.273.8.4660.
Pubmed: 9468526
Janecke AR, Xu R, Steichen-Gersdorf E, Waldegger S, Entenmann A, Giner T, Krainer I, Huber LA, Hess MW, Frishberg Y, Barash H, Tzur S, Schreyer-Shafir N, Sukenik-Halevy R, Zehavi T, Raas-Rothschild A, Mao C, Muller T: Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. Hum Mutat. 2017 Apr;38(4):365-372. doi: 10.1002/humu.23192. Epub 2017 Mar 6.
Pubmed: 28181337
Linhares ND, Arantes RR, Araujo SA, Pena SDJ: Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1. Clin Kidney J. 2018 Aug;11(4):462-467. doi: 10.1093/ckj/sfx130. Epub 2017 Nov 13.
Pubmed: 30090628
Van Veldhoven PP, Gijsbers S, Mannaerts GP, Vermeesch JR, Brys V: Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q22(1). Biochim Biophys Acta. 2000 Sep 27;1487(2-3):128-34. doi: 10.1016/s1388-1981(00)00079-2.
Pubmed: 11018465
Mizutani Y, Kihara A, Igarashi Y: Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation. FEBS Lett. 2004 Apr 9;563(1-3):93-7. doi: 10.1016/S0014-5793(04)00274-1.
Pubmed: 15063729
Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. doi: 10.1038/nature01348. Epub 2003 Jan 1.
Pubmed: 12508121
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