Sign Up for a Free Account
  • Updated 04.30.2024
  • Released 03.30.1995
  • Expires For CME 04.30.2027

Fumarase deficiency

Introduction

Overview

Fumarase deficiency is a rare autosomal recessive disease caused by FH gene mutations that particularly affect the brain. Affected infants typically have microcephaly, ventriculomegaly, abnormal brain structure, severe developmental delay, hypotonia, failure to thrive, seizures, and distinctive facial features. Other signs and symptoms may include hepatosplenomegaly, polycythemia, and leukopenia. There is a high urinary fumaric acid excretion in affected individuals. Affected individuals usually survive only a few months, but a few have lived into early adulthood. No effective treatment is currently available.

Key points

• Fumarase deficiency is a rare autosomal recessive disease caused by FH gene mutations that particularly affect the brain.

• Affected infants typically have microcephaly, ventriculomegaly, abnormal brain structure, severe developmental delay, hypotonia, failure to thrive, seizures, and distinctive facial features. Other signs and symptoms may include hepatosplenomegaly, polycythemia, and leukopenia.

• There is a high urinary fumaric acid excretion in affected individuals.

• Affected individuals usually survive only a few months, but a few have lived into early adulthood.

• No effective treatment is currently available.

Historical note and terminology

Fumarase (fumarate hydratase, EC 4.2.1.2) is an enzyme of the Krebs citric acid cycle that catalyzes the reversible conversion of fumarate to malate (50; 15; 02). Fumarase plays important roles in energy production, DNA repair, and tumor suppression (02).

Krebs citric acid cycle
(Courtesy of Wikimedia Commons. Creative Commons Attribution ShareAlike 3.0 license.)

Fumaric aciduria is a rare metabolic disease caused by a profound decrease of both mitochondrial and cytosolic fumarase activity (05). The first reported cases were described in two adult siblings with mental retardation (72); however, fumarase activity was not measured, and the defect was proposed to be in renal resorption of the acid. In 1986, Zinn and colleagues reported a male infant with severe developmental delay, hypotonia, and progressive microcephaly who died at 8 months of age. Urinary fumarate, succinate, and citrate were elevated and a selective, profound decrease of both mitochondrial and cytosolic fumarase activity was documented (80). Additional patients and sibships have since been reported (41; 70; 20; 17; 49; 09; 36; 13; 26; 78).

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125