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Decreased fumarate hydratase activity

MedGen UID:
343007
Concept ID:
C1853903
Finding
HPO: HP:0003536

Definition

An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of fumarate hydratase activity. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDecreased fumarate hydratase activity

Conditions with this feature

Fumarase deficiency
MedGen UID:
87458
Concept ID:
C0342770
Disease or Syndrome
Fumarate hydratase (FH) deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Dysmorphic facial features include frontal bossing, depressed nasal bridge, and widely spaced eyes. Many affected individuals are microcephalic. A spectrum of brain abnormalities are seen on magnetic resonance imaging, including cerebral atrophy, enlarged ventricles and generous extra-axial cerebral spinal fluid (CSF) spaces, delayed myelination for age, thinning of the corpus callosum, and an abnormally small brain stem. Brain malformations including bilateral polymicrogyria and absence of the corpus callosum can also be observed. Development is severely affected: most affected individuals are nonverbal and nonambulatory, and many die during early childhood. Less severely affected individuals with moderate cognitive impairment and long-term survival have been reported.
Hereditary leiomyomatosis and renal cell cancer
MedGen UID:
353771
Concept ID:
C1708350
Neoplastic Process
FH tumor predisposition syndrome is characterized by cutaneous leiomyomata, uterine leiomyomata (fibroids), and/or renal tumors. Pheochromocytoma and paraganglioma have also been described in a small number of families. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 30 years, increasing in size and number with age. Uterine leiomyomata tend to be numerous and large; age at diagnosis ranges from 18 to 53 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors are usually unilateral, solitary, and aggressive. They are associated with poor survival due to clinical aggressiveness and propensity to metastasize despite small primary tumor size. The median age of detection is approximately age 40 years.

Professional guidelines

PubMed

Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P
Mol Cancer Ther 2009 Mar;8(3):626-35. Epub 2009 Mar 10 doi: 10.1158/1535-7163.MCT-08-1049. PMID: 19276158Free PMC Article

Recent clinical studies

Etiology

Crooks DR, Cawthon GM, Fitzsimmons CM, Perez M, Ricketts CJ, Vocke CD, Yang Y, Middelton L, Nielsen D, Schmidt LS, Tandon M, Merino MJ, Ball MW, Meier JL, Batista PJ, Linehan WM
Hum Mol Genet 2023 Nov 3;32(22):3135-3145. doi: 10.1093/hmg/ddad131. PMID: 37561409Free PMC Article
Peetsold M, Goorden S, Breuning M, Williams M, Bakker J, Jacobs E, Hussaarts-Odijk L, Peeters C
J Child Neurol 2021 Mar;36(4):310-323. Epub 2020 Oct 14 doi: 10.1177/0883073820962931. PMID: 33052056
Teng CC, Kuo HC, Sze CI
Toxicol Appl Pharmacol 2013 Nov 1;272(3):579-90. Epub 2013 Jul 26 doi: 10.1016/j.taap.2013.07.009. PMID: 23891858
Linehan WM, Rouault TA
Clin Cancer Res 2013 Jul 1;19(13):3345-52. Epub 2013 Apr 30 doi: 10.1158/1078-0432.CCR-13-0304. PMID: 23633457Free PMC Article
Sorbi S, Bird ED, Blass JP
Ann Neurol 1983 Jan;13(1):72-8. doi: 10.1002/ana.410130116. PMID: 6219611

Diagnosis

Zheng X, Chen M, Li X, Yang P, Zhao X, Ouyang Y, Yang Z, Liang M, Hou E, Tian Z
Hypertens Res 2019 Nov;42(11):1672-1682. Epub 2019 Jun 24 doi: 10.1038/s41440-019-0290-y. PMID: 31235845
Kamai T, Abe H, Arai K, Murakami S, Sakamoto S, Kaji Y, Yoshida KI
BMC Cancer 2016 Mar 17;16:232. doi: 10.1186/s12885-016-2272-7. PMID: 26983443Free PMC Article
Saini AG, Singhi P
J Child Neurol 2013 Apr;28(4):535-7. Epub 2012 Jul 6 doi: 10.1177/0883073812447286. PMID: 22772160
Wangpaichitr M, Sullivan EJ, Theodoropoulos G, Wu C, You M, Feun LG, Lampidis TJ, Kuo MT, Savaraj N
Mol Cancer Ther 2012 Mar;11(3):604-15. Epub 2012 Jan 16 doi: 10.1158/1535-7163.MCT-11-0599. PMID: 22248473Free PMC Article
Kerrigan JF, Aleck KA, Tarby TJ, Bird CR, Heidenreich RA
Ann Neurol 2000 May;47(5):583-8. PMID: 10805328

Therapy

Teng CC, Kuo HC, Sze CI
Toxicol Appl Pharmacol 2013 Nov 1;272(3):579-90. Epub 2013 Jul 26 doi: 10.1016/j.taap.2013.07.009. PMID: 23891858
Linehan WM, Rouault TA
Clin Cancer Res 2013 Jul 1;19(13):3345-52. Epub 2013 Apr 30 doi: 10.1158/1078-0432.CCR-13-0304. PMID: 23633457Free PMC Article
Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P
Mol Cancer Ther 2009 Mar;8(3):626-35. Epub 2009 Mar 10 doi: 10.1158/1535-7163.MCT-08-1049. PMID: 19276158Free PMC Article
Shindo Y, Akiyama J, Yamazaki Y, Saito K, Takase Y
Exp Gerontol 1991;26(1):29-35. doi: 10.1016/0531-5565(91)90059-u. PMID: 2055281

Prognosis

Edvardson S, Porcelli V, Jalas C, Soiferman D, Kellner Y, Shaag A, Korman SH, Pierri CL, Scarcia P, Fraenkel ND, Segel R, Schechter A, Frumkin A, Pines O, Saada A, Palmieri L, Elpeleg O
J Med Genet 2013 Apr;50(4):240-5. Epub 2013 Feb 7 doi: 10.1136/jmedgenet-2012-101485. PMID: 23393310

Clinical prediction guides

Azzimato V, Chen P, Barreby E, Morgantini C, Levi L, Vankova A, Jager J, Sulen A, Diotallevi M, Shen JX, Miller A, Ellis E, Rydén M, Näslund E, Thorell A, Lauschke VM, Channon KM, Crabtree MJ, Haschemi A, Craige SM, Mori M, Spallotta F, Aouadi M
Gastroenterology 2021 Dec;161(6):1982-1997.e11. Epub 2021 Aug 21 doi: 10.1053/j.gastro.2021.08.030. PMID: 34425095
Podkalicka P, Mucha O, Kruczek S, Biela A, Andrysiak K, Stępniewski J, Mikulski M, Gałęzowski M, Sitarz K, Brzózka K, Józkowicz A, Dulak J, Łoboda A
Biomolecules 2020 Jan 16;10(1) doi: 10.3390/biom10010143. PMID: 31963199Free PMC Article
Shan T, Chen S, Chen X, Lin WR, Li W, Ma J, Wu T, Cui X, Ji H, Li Y, Kang Y
Oncol Rep 2017 Apr;37(4):1971-1979. Epub 2017 Feb 28 doi: 10.3892/or.2017.5479. PMID: 28260082Free PMC Article
Chatterjee I, Maisonneuve E, Ezraty B, Herrmann M, Dukan S
Int J Med Microbiol 2011 Apr;301(4):341-6. Epub 2011 Jan 26 doi: 10.1016/j.ijmm.2010.10.002. PMID: 21273120
Mayr JA, Meierhofer D, Zimmermann F, Feichtinger R, Kögler C, Ratschek M, Schmeller N, Sperl W, Kofler B
Clin Cancer Res 2008 Apr 15;14(8):2270-5. doi: 10.1158/1078-0432.CCR-07-4131. PMID: 18413815

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