fumarate hydratase


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fu·ma·rate hy·dra·tase

(fū'mă-rāt hī'dră-tās), [MIM*136850]
An enzyme catalyzing the reversible interconversion of fumarate and water to malate, a reaction of importance in the tricarboxylic acid cycle. A deficiency will lead to mental retardation.
Synonym(s): fumarase

fumarate hydratase

An enzyme encoded by FH on chromosome 1q42.1, which catalyses the reversible hydration of fumarate to S-malate. The mitochondrial isoform is involved in the Krebs (citric acid) cycle; the cytosol isoform is involved in amino-acid-reductive (carboxylation cycle—CO2 fixation) metabolism.

Abnormal expression
FH mutations can cause fumarase deficiency and lead to progressive encephalopathy, see table.

Molecular defects
Fumarase deficiency in fetus
Polyhydramnios, brain defects.

Fumarase deficiency in neonate
Severe neurologic defects, poor feeding, failure to thrive, and hypotonia; attributed to defects in the mitochondrial and cytosol isoforms.

Fumarate hydratase germ-line mutations trigger an array of tumours: Uterine leiomyomatosis and renal-cell carcinoma (Reed’s syndrome).

fu·ma·rate hy·dra·tase

(fū'măr-āt hī'dră-tās)
An enzyme catalyzing the reversible interconversion of fumaric acid and water to malic acid, a reaction of importance in the tricarboxylic acid cycle. Deficiency leads to mental retardation.
References in periodicals archive ?
Adult Leydig cell tumors of the testis caused by germline fumarate hydratase mutations.
Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma from kidney tumors without FH gene alteration [published online ahead of print February 6, 2018].
Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome.
Immunohistochemical characterization of fumarate hydratase (FH) and succinate dehydrogenase (SDH) in cutaneous leiomyomas for detection of familial cancer syndromes.
Immunohistochemistry for 2-succinocysteine (2SC) and fumarate hydratase (FH) in cutaneous leiomyomas may aid in identification of patients with HLRCC (hereditary leiomyomatosis and renal cell carcinoma syndrome).
The cutaneous leiomyomata (A) seen in patients with HLRCC usually do not show distinct morphologic features but often demonstrate loss of fumarate hydratase (FH) expression by immunohistochemistry (B).
In addition, HLRCC-associated RCC may mimic collecting duct carcinoma with neoplastic tubules demonstrating an infiltrative growth pattern (E); however, fumarate hydratase expression is lost in HLRCC-associated RCC (F) but retained in healthy kidney (F, inset) (hematoxylin-eosin, original magnifications X200 [A and E], X400 [B and D], and X100 [C]; fumarate hydratase, original magnifications X400 [F] and X200 [F, inset]).
Although there is some morphologic resemblance to tubulocystic carcinoma in focal areas, presence of poorly differentiated foci (B) should prompt consideration of HLRCC and evaluation of fumarate hydratase (FH) status (B-inset, loss of FH expression by IHC).
Type 2 papillary renal cell carcinoma (RCC) can show a solid growth pattern with prominent nucleoli (A), which may raise concern for hereditary leiomyomatosis and RCC syndrome (HLRCC)-associated RCC; however, fumarate hydratase (FH) expression is retained in papillary RCC (B).