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Genetic and Rare Diseases Information Center (GARD)

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Fumarase deficiency


Other Names for this Disease
  • Fumarate hydratase deficiency
  • Fumaric aciduria
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Overview



What is fumarase deficiency?

What are the signs and symptoms of fumarase deficiency?

What causes fumarase deficiency?

How might fumarase deficiency be treated?


What is fumarase deficiency?

Fumarase deficiency is an inherited condition that primarily affects the nervous system, especially the brain. Affected infants may have microcephaly, abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), failure to thrive, seizures, and/or distinctive facial features. Other signs and symptoms may include hepatosplenomegaly, an excess of red blood cells (polycythemia), and/or or deficiency of white blood cells (leukopenia). Affected individuals usually survive only a few months, but a few have lived into early adulthood. This condition is caused by mutations in the FH gene and is inherited in an autosomal recessive manner.[1] No effective treatment is currently available.[2]
Last updated: 11/6/2012

What are the signs and symptoms of fumarase deficiency?

Most newborns with fumarase deficiency show severe neurologic abnormalities, including poor feeding, failure to thrive, and poor muscle tone (hypotonia). Early-onset infantile encephalopathy (altered brain structure or function), seizures, and severe developmental delay with microcephaly are also common. Other signs and symptoms may include infantile spasms, abnormal posturing of the limbs, and autistic features. Distinctive facial features have been reported in some affected individuals and have included an unusually prominent forehead (frontal bossing); low-set ears; a small jaw (micrognathia); widely-spaced eyes (ocular hypertelorism); depressed nasal bridge; and high-arched palate.[2]

Other findings in affected individuals can include neonatal polycythemia (an excess of red blood cells); leukopenia (deficiency of white blood cells); neutropenia; enlarged liver and spleen (hepatosplenomegaly); and pancreatitis.[2]

Many children with this condition do not survive infancy or childhood. Those surviving beyond childhood have severe psychomotor deficits.[2]
Last updated: 11/6/2012

What causes fumarase deficiency?

Mutations in the FH gene cause fumarase deficiency. The FH gene provides instructions for making an enzyme called fumarase, which participates in a series of reactions allowing cells to use oxygen and generate energy. Mutations in the FH gene disrupt the enzyme's ability to do its job. Disruption of the process that generates energy for cells is particularly harmful to cells in the developing brain, thus resulting in the signs and symptoms of fumarase deficiency.
Last updated: 11/6/2012

How might fumarase deficiency be treated?

There is currently no effective treatment for fumarase deficiency. Nutritional intervention may be appropriate for children with feeding difficulties. Physical therapy and wheelchairs can also be useful for some individuals.[2]
Last updated: 11/6/2012

References
  1. Fumarase deficiency. Genetics Home Reference. April 2008; http://ghr.nlm.nih.gov/condition/fumarase-deficiency. Accessed 1/20/2012.
  2. Vivian E Shih and Roseann Mandell. Fumarate Hydratase Deficiency. GeneReviews. June 2, 2009; http://www.ncbi.nlm.nih.gov/books/NBK1506/. Accessed 11/6/2012.
  3. Fumarase deficiency. Genetics Home Reference. April 2008; http://ghr.nlm.nih.gov/condition/fumarase-deficiency. Accessed 11/6/2012.