GABA-transaminase deficiency
GABA-transaminase deficiency is a rare, severe brain disease beginning in infancy that causes recurrent seizures, developmental delays, and accelerated physical growth.
Overview
GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Children with this disorder have profoundly impaired development. Most do not achieve normal developmental milestones of infancy, such as following others' movement with their eyes or sitting unassisted. Individuals with this disorder usually do not survive past the first 2 years of life, but some live longer into childhood.
Symptoms and Clinical Features
Babies affected by this condition experience a range of severe neurological and physical symptoms, which include:
- Recurrent seizures (epilepsy)
- Uncontrolled limb movements (choreoathetosis)
- Exaggerated reflexes (hyperreflexia)
- Weak muscle tone (hypotonia)
- Excessive sleepiness (hypersomnolence)
- Accelerated linear growth (growing faster in length than usual)
- Feeding problems and a failure to gain weight as quickly as expected (failure to thrive)
Frequency
GABA-transaminase deficiency is a very rare disorder. Only a small number of affected individuals have been described in the medical literature.
Causes and Risk Factors
The condition is caused by mutations in the ABAT gene, which provides instructions for making the GABA-transaminase enzyme. This enzyme is responsible for breaking down a brain chemical (neurotransmitter) called GABA when it is no longer needed.
GABA is an inhibitory neurotransmitter that normally helps slow down brain cell activity to prevent the brain from being overloaded with too many signals. Mutations in the ABAT gene lead to a shortage of functional GABA-transaminase enzyme. Consequently, GABA is not properly broken down, causing this neurotransmitter and another molecule called beta-alanine to accumulate abnormally in brain cells.
This accumulation alters the balance of neurotransmitters in the brain, leading to the characteristic neurological problems of the disorder. Additionally, excess GABA leads to the abnormal release of a protein necessary for the growth of the body's bones and tissues, resulting in accelerated linear growth.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- 4 alpha aminobutyrate transaminase deficiency
- ABAT deficiency
- GABA transaminase deficiency
- GABA transferase deficiency
- GABA-T deficiency
- Gamma aminobutyrate transaminase deficiency
- Gamma aminobutyric acid transaminase deficiency
- Gamma-aminobutyrate transaminase deficiency
- Gamma-aminobutyric acid transaminase deficiency