Glutaric Aciduria Type 1
Glutaric aciduria type 1 is a rare inherited metabolic disorder caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase, which is responsible for breaking down certain amino acids. When this enzyme is absent or malfunctioning, glutaric acid and related compounds accumulate in the body, particularly in the brain, leading to neurological damage. Glutaric aciduria type 1 typically presents in infancy or early childhood and, without early diagnosis and management, can result in severe motor impairment and other lifelong complications.
As a disorder of amino acid metabolism, glutaric aciduria type 1 is classified under the group of conditions known as organic acidemias. Although considered rare, its severity and the possibility of preventing neurological damage through early dietary and medical intervention make awareness and timely diagnosis essential.
What Happens in the Body?
Glutaric aciduria type 1 results from mutations in the GCDH gene, which encodes the enzyme glutaryl-CoA dehydrogenase. This enzyme plays a vital role in breaking down the amino acids lysine, hydroxylysine, and tryptophan.
In the absence of normal enzyme function:
Toxic compounds like glutaric acid, 3-hydroxyglutaric acid, and glutaconic acid build up in the body
These substances accumulate particularly in the basal ganglia—a part of the brain involved in movement control
As a result, brain cells become damaged, often leading to dystonia, spasticity, and motor regression
The severity of neurological outcomes depends on how early the condition is diagnosed and whether treatment begins before a “metabolic crisis” occurs.
How Common Is It?
Glutaric aciduria type 1 is estimated to affect approximately 1 in 100,000 people worldwide. However, higher rates have been reported in certain populations, including:
The Amish and Mennonite communities of North America
Some regions of Sweden
Middle Eastern and North African populations where consanguineous marriages are more common
In these groups, carrier frequency may be significantly higher, and genetic counselling becomes particularly important.
Onset and Presentation
There are three general presentations of glutaric aciduria type 1:
1. Asymptomatic (Detected through Screening)
Newborn screening identifies elevated markers
No signs or symptoms at diagnosis
Early treatment can completely prevent damage
2. Infantile-Onset
Appears between 3 and 36 months
Often triggered by febrile illness, immunisation, or fasting
Presents with sudden loss of motor skills, irritability, and hypotonia
Progresses to dystonic cerebral palsy if not treated promptly
3. Late-Onset
Appears after age 3, sometimes during adolescence
May cause milder neurological issues such as learning difficulties or tremors
Rare but possible in undiagnosed or mismanaged individuals
Key Symptoms and Signs
The condition can be variable, but typical symptoms include:
Macrocephaly (abnormally large head circumference)
Seizures
Hypotonia (reduced muscle tone)
Delayed development or regression of skills
Dystonia (involuntary muscle contractions)
Choreoathetosis (irregular movements)
In infants who experience a metabolic crisis, symptoms may progress quickly and leave lasting neurological damage.
Diagnosis and Screening
Most developed countries now include glutaric aciduria type 1 in their newborn screening panels. Diagnosis involves:
Tandem mass spectrometry to detect elevated levels of glutaric acid and related metabolites
Urine organic acid analysis
Molecular genetic testing to confirm mutations in the GCDH gene
Enzyme assay (when available) to measure glutaryl-CoA dehydrogenase activity
Early detection via newborn screening allows for presymptomatic treatment and dramatically improves outcomes.
Treatment Goals
The aim of treatment is to:
Prevent metabolic crises
Avoid neurological deterioration
Ensure normal growth and development
Manage complications like movement disorders or seizures
A coordinated care team typically includes a metabolic specialist, dietitian, neurologist, and paediatrician.
Conclusion | Glutaric Aciduria Type 1
Glutaric aciduria type 1 is a serious but manageable metabolic disorder when detected early. With timely diagnosis through newborn screening and prompt initiation of treatment, individuals with glutaric aciduria type 1 can lead significantly healthier lives. Without intervention, however, irreversible neurological damage is likely. Raising awareness among healthcare providers and parents is key to preventing long-term disability.
