Definition
Fumarase deficiency, also known as fumaric aciduria, is a rare metabolic disorder characterized by the impaired activity of the enzyme fumarase. This enzyme is involved in a critical step of the Krebs cycle, also known as the citric acid cycle, which plays a vital role in cellular energy production.
Cause
Fumarase deficiency is an autosomal recessive disorder, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The disorder is caused by mutations in the FH gene, which provides instructions for producing the fumarase enzyme. These mutations result in the partial or complete loss of enzyme activity.
Symptoms
The symptoms of fumarase deficiency can vary widely among affected individuals. Common signs and symptoms may include:
- Developmental delays
- Feeding difficulties
- Hypotonia (low muscle tone)
- Seizures
- Intellectual disability
- Failure to thrive
- Mental retardation
In severe cases, fumarase deficiency can also lead to life-threatening complications, such as brain malformations and mitochondrial dysfunction.
Diagnosis
Diagnosing fumarase deficiency usually involves a combination of clinical evaluation, biochemical testing, and genetic analysis. The presence of elevated levels of fumaric acid in the urine and/or low levels of fumarase activity in the blood can help confirm the diagnosis. Genetic testing can identify specific mutations in the FH gene.
Treatment
Currently, there is no cure for fumarase deficiency. Treatment is focused on managing the symptoms and preventing complications. This may involve a combination of dietary interventions, physical therapy, and medications to control seizures or other associated medical conditions.
Prognosis
The prognosis for individuals with fumarase deficiency can vary depending on the severity of the condition. In severe cases, the disorder is often life-threatening, with affected individuals experiencing significant neurological impairment and reduced life expectancy. However, milder forms of the condition have been reported where individuals may have better developmental outcomes and a relatively normal lifespan.