Defisiensi fumarase

Defisiensi fumarase
Defisiensi fumarase
	Fumarate diubah menjadi malate oleh fumarase
Informasi umum

Defisiensi fumarase atau aciduria fumarik adalah penyakit metabolis resesif autosomal yang dipicu oleh kekurangan enzim fumarat hidratase, yang dapat diketahui dari konsentrasi kandungan asam fumarik di dalam urin. Defisiensi fumarase dapat mengakibatkan ensefalopati,^[1] keterbelakangan mental, bentuk wajah yang tidak biasa, malformasi otak, dan serangan epilepsi^[2] yang dipicu oleh rendahnya kandungan fumarase di dalam sel.

Patofisiologi

Defisiensi fumarase disebabkan oleh mutasi dalam gen fumarat hidratase (FH) pada manusia, yang menyandikan enzim yang mengubah fumarat menjadi malat dalam mitokondria. Alel mutan gen FH lain yang terletak di kromosom 1 pada posisi 1q42.1 dapat memicu leiomioma dan kanker sel ginjal.^[3]

Penyakit ini bersifat resesif autosomal,^[4] sehingga seorang individu harus memperoleh alel mutan dari kedua orang tua. Sejumlah anak yang didiagnosis mengidap penyakit ini terlahir dari orang tua yang merupakan sepupu.^[5]^[6] Penyakit ini juga dapat diturunkan dalam kondisi isodisomi uniparental.^[7]

Epidemiologi

Defisiensi fumarase merupakan penyakit yang sangat langka - hingga sekitar tahun 1990, hanya terdapat sekitar 13 kasus yang telah didiagnosis di seluruh dunia. Namun, 20 kasus telah tercatat di kota kembar Colorado City, Arizona dan Hildale, Utah pada komunitas Gereja Mormon Fundamentalis yang melakukan perkawinan sekerabat.^[8]^[9]^[10]^[11]

Referensi

^ Bayley, Jean-Pierre; Launonen, Virpi; Tomlinson, Ian P.M. (25 March 2008). "The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency". BMC Med. Genet. 9 (1): 20. doi:10.1186/1471-2350-9-20. PMC 2322961  . PMID 18366737.
^ Kerrigan, John F.; Aleck, Kirk A.; Tarby, Theodore J.; Bird, C. Roger; Heidenreich, Randall A. (May 2000) [3 May 2001]. "Fumaric aciduria: clinical and imaging features". Ann. Neurol. 47 (5): 583–8. doi:10.1002/1531-8249(200005)47:5<583::AID-ANA5>3.0.CO;2-Y. PMID 10805328.
^ Online Mendelian Inheritance in Man (OMIM) Deficiency -606812
^ Gellera, C.; Uziel, G.; Rimoldi, M.; Zeviani, M.; Laverda, A.; Carrara, F.; DiDonato, S. (March 1990). "Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes". Neurology. 40 (3 Part 1): 495–499. doi:10.1212/wnl.40.3_part_1.495. PMID 2314594.
^ Petrova-Benedict, R.; Robinson, B.H.; Stacey, T.E.; Mistry, J.; Chalmers, R.A. (1987). "Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing". Am. J. Hum. Genet. 40 (3): 257–266. PMC 1684096  . PMID 3578275.
^ Bourgeron, T.; Chretien, D.; Poggi-Bach, J.; Doonan, S.; Rabier, D.; Letouzé, P.; Munnich, A.; Rötig, A.; Landrieu, P.; Rustin, P. (June 1994). "Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency". J. Clin. Invest. 93 (6): 2514–2518. doi:10.1172/JCI117261. PMC 294471  . PMID 8200987.
^ Zeng, Wen-Qi; Gao, Hanlin; Brueton, Louise; Hutchin, Tim; Gray, George; Chakrapani, Anupam; Olpin, Simon; Shih, Vivian E. (1 May 2006) [30 March 2006]. "Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1". Am. J. Med. Genet. A. 140A (9): 1004–1009. doi:10.1002/ajmg.a.31186. PMID 16575891.
^ Dougherty, John (December 29, 2005). "Forbidden Fruit:Inbreeding among polygamists along the Arizona-Utah border is producing a caste of severely retarded and deformed children". The Phoenix New Times News. hlm. 2. Diarsipkan dari versi asli tanggal 2015-04-20. Diakses tanggal 2017-08-14.
^ "Mormon Sect's Polygamy Causes Most Of The World's Fumarase Deficiency Cases". Digital Journal.
^ Hollenhorst, John (February 8, 2006). "Birth defect is plaguing children in FLDS towns: Fumarase Deficiency afflicts 20, is linked to marriages of close Kin". Deseret News.
^ Szep, Jason (June 14, 2007). "Polygamist community faces rare genetic disorder". Reuters.

Bacaan lanjut

Pithukpakorn, Manop; Toro, Jorge R. (November 2, 2010) [July 31, 2006]. "Hereditary Leiomyomatosis and Renal Cell Cancer". GeneReviews. Seattle WA: University of Washington. PMID 20301430.

Pranala luar

Mitochondrial Disorders: Fumarase Deficiency at Washington University, St. Louis, Missouri

Artikel bertopik penyakit ini adalah sebuah rintisan. Anda dapat membantu Wikipedia dengan mengembangkannya.

[pmid18366737-1] Bayley, Jean-Pierre; Launonen, Virpi; Tomlinson, Ian P.M. (25 March 2008). "The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency". BMC Med. Genet. 9 (1): 20. doi:10.1186/1471-2350-9-20. PMC 2322961  . PMID 18366737.

[pmid10805328-2] Kerrigan, John F.; Aleck, Kirk A.; Tarby, Theodore J.; Bird, C. Roger; Heidenreich, Randall A. (May 2000) [3 May 2001]. "Fumaric aciduria: clinical and imaging features". Ann. Neurol. 47 (5): 583–8. doi:10.1002/1531-8249(200005)47:5<583::AID-ANA5>3.0.CO;2-Y. PMID 10805328.

[3] Online Mendelian Inheritance in Man (OMIM) Deficiency -606812

[pmid2314594-4] Gellera, C.; Uziel, G.; Rimoldi, M.; Zeviani, M.; Laverda, A.; Carrara, F.; DiDonato, S. (March 1990). "Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes". Neurology. 40 (3 Part 1): 495–499. doi:10.1212/wnl.40.3_part_1.495. PMID 2314594.

[pmid3578275-5] Petrova-Benedict, R.; Robinson, B.H.; Stacey, T.E.; Mistry, J.; Chalmers, R.A. (1987). "Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing". Am. J. Hum. Genet. 40 (3): 257–266. PMC 1684096  . PMID 3578275.

[pmid8200987-6] Bourgeron, T.; Chretien, D.; Poggi-Bach, J.; Doonan, S.; Rabier, D.; Letouzé, P.; Munnich, A.; Rötig, A.; Landrieu, P.; Rustin, P. (June 1994). "Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency". J. Clin. Invest. 93 (6): 2514–2518. doi:10.1172/JCI117261. PMC 294471  . PMID 8200987.

[pmid16575891-7] Zeng, Wen-Qi; Gao, Hanlin; Brueton, Louise; Hutchin, Tim; Gray, George; Chakrapani, Anupam; Olpin, Simon; Shih, Vivian E. (1 May 2006) [30 March 2006]. "Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1". Am. J. Med. Genet. A. 140A (9): 1004–1009. doi:10.1002/ajmg.a.31186. PMID 16575891.

[Dougherty2005-8] Dougherty, John (December 29, 2005). "Forbidden Fruit:Inbreeding among polygamists along the Arizona-Utah border is producing a caste of severely retarded and deformed children". The Phoenix New Times News. hlm. 2. Diarsipkan dari versi asli tanggal 2015-04-20. Diakses tanggal 2017-08-14.

[digitaljournal-9] "Mormon Sect's Polygamy Causes Most Of The World's Fumarase Deficiency Cases". Digital Journal.

[10] Hollenhorst, John (February 8, 2006). "Birth defect is plaguing children in FLDS towns: Fumarase Deficiency afflicts 20, is linked to marriages of close Kin". Deseret News.

[11] Szep, Jason (June 14, 2007). "Polygamist community faces rare genetic disorder". Reuters.

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