J u m p t o c o n t e n t
M a i n m e n u
M a i n m e n u
N a v i g a t i o n
● M a i n p a g e
● C o n t e n t s
● C u r r e n t e v e n t s
● R a n d o m a r t i c l e
● A b o u t W i k i p e d i a
● C o n t a c t u s
● D o n a t e
C o n t r i b u t e
● H e l p
● L e a r n t o e d i t
● C o m m u n i t y p o r t a l
● R e c e n t c h a n g e s
● U p l o a d f i l e
S e a r c h
Search
A p p e a r a n c e
● C r e a t e a c c o u n t
● L o g i n
P e r s o n a l t o o l s
● C r e a t e a c c o u n t
● L o g i n
P a g e s f o r l o g g e d o u t e d i t o r s l e a r n m o r e
● C o n t r i b u t i o n s
● T a l k
( T o p )
1
P r e s e n t a t i o n
2
P a t h o p h y s i o l o g y
3
D i a g n o s i s
4
T r e a t m e n t
5
E p i d e m i o l o g y
6
S e e a l s o
7
R e f e r e n c e s
8
F u r t h e r r e a d i n g
9
E x t e r n a l l i n k s
T o g g l e t h e t a b l e o f c o n t e n t s
F u m a r a s e d e f i c i e n c y
4 l a n g u a g e s
● ا ل ع ر ب ي ة
● F r a n ç a i s
● B a h a s a I n d o n e s i a
● I t a l i a n o
E d i t l i n k s
● A r t i c l e
● T a l k
E n g l i s h
● R e a d
● E d i t
● V i e w h i s t o r y
T o o l s
T o o l s
A c t i o n s
● R e a d
● E d i t
● V i e w h i s t o r y
G e n e r a l
● W h a t l i n k s h e r e
● R e l a t e d c h a n g e s
● U p l o a d f i l e
● S p e c i a l p a g e s
● P e r m a n e n t l i n k
● P a g e i n f o r m a t i o n
● C i t e t h i s p a g e
● G e t s h o r t e n e d U R L
● D o w n l o a d Q R c o d e
● W i k i d a t a i t e m
P r i n t / e x p o r t
● D o w n l o a d a s P D F
● P r i n t a b l e v e r s i o n
A p p e a r a n c e
F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
Fumarase deficiency (or fumaric aciduria ) is an exceedingly rare autosomal recessive metabolic disorder in the Krebs cycle , characterized by a deficiency of the enzyme fumarate hydratase , which causes a buildup of fumaric acid in the urine and a deficiency of malate . Only 13 cases were known worldwide in 1990, after which a cluster of 20 cases was documented in a community in Arizona, US that has practiced successive endogamy .
Presentation [ edit ]
Fumarase deficiency causes encephalopathy ,[2] severe intellectual disabilities , unusual facial features, brain malformation, and epileptic seizures [3] due to an abnormally low amount of fumarase in cells. It can initially present with polyhydramnios on prenatal ultrasound. Affected neonates may demonstrate nonspecific signs of poor feeding and hypotonia . Laboratory findings in neonates may indicate polycythemia , leukopenia , or neutropenia . As they age, neurological deficits begin to manifest with seizures, dystonias , and severe developmental delay.[4]
Pathophysiology [ edit ]
Fumarase deficiency is caused by a mutation in the fumarate hydratase (FH ) gene in humans, which encodes the enzyme that converts fumarate to malate in the mitochondria . Other mutant alleles of the FH gene, located on human Chromosome 1 at position 1q42.1, cause multiple cutaneous and uterine leiomyomata , hereditary leiomyomatosis and renal cell cancer .[5] Fumarase deficiency is one of the few known deficiencies of the Krebs cycle or tricarboxylic acid cycle , the main enzymatic pathway of cellular aerobic respiration .[6]
Fumarase deficiency has an autosomal recessive pattern of inheritance .
The condition is an autosomal recessive disorder,[7] and it is therefore usually necessary for an affected individual to receive the mutant allele from both parents. A number of children diagnosed with the disorder have been born to parents who were first cousins .[8] [9] It can also be associated with uniparental isodisomy .[10]
Diagnosis [ edit ]
This section is empty. You can help by
adding to it .
(July 2017 )
Treatment [ edit ]
Epidemiology [ edit ]
Fumarase deficiency is extremely rare – until around 1990 there had only been 13 diagnosed and identified cases worldwide.[citation needed ]
A cluster of 20 cases has since been documented in the twin towns of Colorado City, Arizona and Hildale, Utah , both of which were formerly known as "Short Creek" (or the Short Creek Community ). The two towns combine to form a community of 10,000 members of the Fundamentalist Church of Jesus Christ of Latter Day Saints (FLDS) who have a history of practicing successive endogamy, or marriage within their own communities.[11] [12] [13] [14] Nicknamed "Polygamist's Down's ", the syndrome has been blamed on cousin marriage , but in a larger sense is related to the reproductive isolation of a community among whom 85% are blood relatives of John Y. Barlow and/or Joseph Smith Jessop (the cofounders of the Short Creek Community).[12]
Since the initial cluster from FLDS communities were reported, it is now estimated that there are 100 documented cases worldwide.[15]
See also [ edit ]
References [ edit ]
^ 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 . S2CID 10448322 .
^ Ewbank, Clifton; Kerrigan, John F.; Aleck, Kirk (April 4, 2013) [July 5, 2006]. "Fumarate Hydratase Deficiency" . GeneReviews . Seattle WA: University of Washington . PMID 20301679 .
^ Online Mendelian Inheritance in Man (OMIM): Fumarase Deficiency - 606812
^ Devlin, Thomas M. (2006). Textbook of biochemistry: with clinical correlations . New York: John Wiley. p. 546. ISBN 978-0-471-67808-3 .
^ 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 . S2CID 1292556 .
^ 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 . S2CID 38553151 .
^ 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 . p. 2. Archived from the original on 2015-04-20. Retrieved 2008-04-16 .
^ a b "Mormon Sect's Polygamy Causes Most Of The World's Fumarase Deficiency Cases" . Digital Journal . 2007-06-14.
^ 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 .
^ Fumarase deficiency MedlinePlus accessed via Internet June 20, 2022
Further reading [ edit ]
External links [ edit ]
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=Fumarase_deficiency&oldid=1190169114 "
C a t e g o r i e s :
● A m i n o a c i d m e t a b o l i s m d i s o r d e r s
● A u t o s o m a l r e c e s s i v e d i s o r d e r s
● R a r e d i s e a s e s
● T C A a n d E T C m e t a b o l i s m d i s o r d e r s
● F u n d a m e n t a l i s t C h u r c h o f J e s u s C h r i s t o f L a t t e r - D a y S a i n t s
● D i s o r d e r s c a u s i n g s e i z u r e s
H i d d e n c a t e g o r i e s :
● A r t i c l e s w i t h s h o r t d e s c r i p t i o n
● S h o r t d e s c r i p t i o n m a t c h e s W i k i d a t a
● S h o r t d e s c r i p t i o n i s d i f f e r e n t f r o m W i k i d a t a
● A r t i c l e s t o b e e x p a n d e d f r o m J u l y 2 0 1 7
● A l l a r t i c l e s t o b e e x p a n d e d
● A r t i c l e s w i t h e m p t y s e c t i o n s f r o m J u l y 2 0 1 7
● A l l a r t i c l e s w i t h e m p t y s e c t i o n s
● A r t i c l e s u s i n g s m a l l m e s s a g e b o x e s
● A l l a r t i c l e s w i t h u n s o u r c e d s t a t e m e n t s
● A r t i c l e s w i t h u n s o u r c e d s t a t e m e n t s f r o m S e p t e m b e r 2 0 2 0
● T h i s p a g e w a s l a s t e d i t e d o n 1 6 D e c e m b e r 2 0 2 3 , a t 0 9 : 4 5 ( U T C ) .
● T e x t i s a v a i l a b l e u n d e r t h e C r e a t i v e C o m m o n s A t t r i b u t i o n - S h a r e A l i k e L i c e n s e 4 . 0 ;
a d d i t i o n a l t e r m s m a y a p p l y . B y u s i n g t h i s s i t e , y o u a g r e e t o t h e T e r m s o f U s e a n d P r i v a c y P o l i c y . W i k i p e d i a ® i s a r e g i s t e r e d t r a d e m a r k o f t h e W i k i m e d i a F o u n d a t i o n , I n c . , a n o n - p r o f i t o r g a n i z a t i o n .
● P r i v a c y p o l i c y
● A b o u t W i k i p e d i a
● D i s c l a i m e r s
● C o n t a c t W i k i p e d i a
● C o d e o f C o n d u c t
● D e v e l o p e r s
● S t a t i s t i c s
● C o o k i e s t a t e m e n t
● M o b i l e v i e w