The following information may help to address your question:
What is fumarase deficiency?
Fumarase deficiency is an
inherited condition that affects the brain and other parts of the nervous system. Signs and symptoms may include a small head (
microcephaly), severe
developmental delay, poor feeding, weak muscle tone (
hypotonia),
failure to thrive,
seizures, and distinctive facial features.
[1][2] Most people with this deficiency are not able to speak or walk.
[2][3] A variety of brain abnormalities may be detected on
MRI.
[3] Fumarase deficiency is caused by
mutations in the
FH gene and inheritance is
autosomal recessive.
[1][2][3] Unfortunately, there is no effective treatment at this time.
[3] Management aims to improve symptoms and increase quality of life. Many children with fumarase deficiency do not survive past early childhood, but some are less severely affected, have mild cognitive impairment, and survive beyond this time.
[2][3]
Last updated: 2/15/2018
What are the signs and symptoms of fumarase deficiency?
Most newborns with fumarase deficiency have severe neurologic abnormalities including poor feeding,
failure to thrive, and poor muscle tone (hypotonia). Early-onset infantile
encephalopathy (abnormal brain structure or function), seizures,
microcephaly, and severe developmental delay are also common. Most children with fumarase deficiency do not learn to walk and talk. Some also have polycythemia (an excess of
red blood cells), recurrent vomiting, or
pancreatitis. Distinctive facial features that may be present include a prominent forehead (frontal bossing), depressed nasal bridge, and widely-spaced eyes.
[3]
A variety of brain abnormalities may be identified on brain MRI. These may include
cerebral atrophy (loss of neurons and their connections to each other), enlarged ventricles (cavities where cerebrospinal fluid is produced), thinning or
absence (agenesis) of the corpus callosum, and an abnormally small
brain stem (the part of the brain that connects to the spinal cord).
[3]
Last updated: 2/19/2018
What causes fumarase deficiency?
Fumarase deficiency is caused by mutations in the
FH gene.
[1][3] This gene gives the body instructions for making an
enzyme called fumarase, which helps
cells use oxygen and make energy. Mutations in the gene interfere with the enzyme's function. Making energy is particularly important to cells during brain development, so when the enzyme does not work properly, the brain does not develop properly, leading to many of the signs and symptoms of fumarase deficiency.
[1]
Last updated: 2/19/2018
How might fumarase deficiency be treated?
Currently there is no effective treatment for fumarase deficiency. The goal of management is to improve symptoms, prevent complications, and increase quality of life. Examples of management options include:
[3]
- Standard anticonvulsant medications for seizures.
- Placement of a feeding tube (if needed) for optimal nutrition and to prevent aspiration.
- Special needs services for support with motor, language, and social development.
Last updated: 2/19/2018
How many people have fumarase deficiency?
Fumarase deficiency is a rare disease, with around 100 reported cases worldwide as of 2017.
[1][3] The disease occurs in people of different ethnic backgrounds, but several people with fumarase deficiency were from an isolated religious community in the southwestern United States (around the border of northern Arizona and southern Utah).
[1] The increased frequency in this area is thought to be due to a
founder effect in closed, polygamist communities in which marriage between relatives is more common.
[4]
Last updated: 2/19/2018
How can I find individuals or families affected by fumarase deficiency?
You may be able to connect with individuals and/or families affected by fumarase deficiency through
Climb, the National Information Centre for
Metabolic Diseases. This organization works on behalf of children, young people, adults and families affected by metabolic disease. They have a
Climb Family Contacts Network, which aims to help reduce the sense of isolation felt by many families affected by a rare disease, giving families the opportunity to share experiences, information and advice.
Last updated: 11/7/2012
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GARD Information Specialist
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