Glutaric Aciduria Type I
Description
Glutaric Aciduria Type I (GA1), also known as Glutaric Acidemia Type I, is a rare inherited metabolic disorder that affects the brain. It is caused by a deficiency in the enzyme glutaryl-CoA dehydrogenase (GCDH), which plays a crucial role in breaking down certain amino acids. This deficiency leads to a buildup of toxic substances in the body, particularly glutaric acid, which can damage the brain, especially during periods of illness or stress.
Genes Involved
GA1 is caused by mutations in the GCDH gene, located on chromosome 19. This gene provides instructions for making the GCDH enzyme.
Recognizing the Signs and Symptoms
Symptoms of GA1 usually appear in the first few months of life. They can include:
- Delayed development: Slowness in reaching developmental milestones, such as rolling over, sitting up, or crawling.
- Seizures: Episodes of uncontrolled muscle activity.
- Movement problems: Difficulties with coordination and balance.
- Hypotonia: Decreased muscle tone, leading to floppy limbs.
- Dyskinesia: Involuntary movements of the body, often described as twitching or jerking.
- Behavioral problems: Irritability, aggression, or difficulty concentrating.
- Encephalopathy: A brain disorder that can lead to confusion, drowsiness, and seizures.
It is important to note that some infants with GA1 may not experience any symptoms until later in childhood or adolescence.
Causes
Glutaric Aciduria Type I is caused by a deficiency in the enzyme glutaryl-CoA dehydrogenase (GCDH). This deficiency is due to mutations in the GCDH gene. Without a properly functioning GCDH enzyme, the body cannot break down certain amino acids, leading to a buildup of toxic substances, particularly glutaric acid, which can damage the brain.
Inheritance/recurrence risk
GA1 is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. If both parents carry one copy of the mutated gene, they have a 25% chance of having a child with GA1, a 50% chance of having a child who is a carrier, and a 25% chance of having a child who does not carry the gene. Carrier parents are usually healthy and may not know they carry the mutated gene until they have a child with GA1.
