Diagnosis of Glutaric Aciduria Type 1
The diagnosis of glutaric aciduria type 1 is essential for preventing serious neurological complications and enabling early treatment. In many countries, the diagnosis of glutaric aciduria type 1 is now possible through routine newborn screening, which has significantly improved outcomes by identifying affected infants before symptoms develop.
A deficiency in the enzyme glutaryl-CoA dehydrogenase causes glutaric aciduria type 1, leading to the accumulation of toxic compounds in the body. If undetected, these substances can damage the brain, particularly the basal ganglia, leading to permanent motor disability. Early and accurate diagnosis ensures timely interventions that can prevent irreversible injury.
Newborn Screening
In countries with comprehensive newborn screening programmes, diagnosis usually begins in the first days of life:
Dried blood spot testing (heel prick test) uses tandem mass spectrometry to detect elevated levels of glutaric acid derivatives
Screening typically identifies markers such as glutaric acid, 3-hydroxyglutaric acid, and C5DC-carnitine
Positive results trigger confirmatory testing and immediate referral to a metabolic specialist
Early detection allows treatment to begin before a metabolic crisis occurs, offering the best chance at normal development.
Biochemical Testing
In addition to screening, diagnostic biochemical tests confirm the presence of the condition:
1. Urine Organic Acid Analysis
Performed using gas chromatography–mass spectrometry (GC-MS)
Detects elevated glutaric acid, 3-hydroxyglutaric acid, and glutaconic acid
2. Plasma Acylcarnitine Profile
Elevated glutarylcarnitine (C5DC) is a hallmark of the condition
Supports the urine analysis findings
These tests are non-invasive and form the cornerstone of diagnosis in symptomatic individuals and newborns flagged during screening.
Enzyme Assay
Where available, direct measurement of glutaryl-CoA dehydrogenase activity in:
Fibroblasts (from a skin biopsy)
White blood cells (leukocytes)
Clinicians use this functional assay to confirm the deficiency and possibly predict disease severity, but genetic testing is now more common and less invasive.
Genetic Testing
Molecular genetic analysis of the GCDH gene:
Confirms the presence of pathogenic mutations
Can detect carriers within the family
Supports prenatal diagnosis in future pregnancies
Identifies genotype–phenotype correlations that may influence management
Researchers have reported over 200 mutations, with some causing milder or more severe clinical outcomes
Neuroimaging
For children presenting with symptoms before diagnosis, MRI of the brain can be useful:
Shows characteristic changes in the basal ganglia
May reveal widening of the Sylvian fissures (open operculum)
Helps differentiate glutaric aciduria type 1 from other neurological conditions
Doctors typically do not require an MRI if screening confirms the diagnosis and the patient shows no symptoms.
Differential Diagnosis
Symptoms such as macrocephaly, dystonia, and regression may also occur in other conditions. Therefore, it is important to rule out:
Other organic acidurias, such as methylmalonic or propionic aciduria
Mitochondrial disorders
Perinatal brain injury
Cerebral palsy
Doctors ensure accurate diagnosis so they can quickly implement targeted dietary and emergency treatment plans.
Family Testing and Genetic Counselling
Doctors recommend family screening as soon as they confirm a diagnosis:
Doctors can test parents and siblings to determine their carrier status
Genetic counselling provides information on recurrence risks
Genetic counselors can offer prenatal testing or preimplantation genetic diagnosis (PGD) for future pregnancies
Counselling also helps families understand the implications of the diagnosis and the importance of treatment adherence.
Follow-Up After Diagnosis
Following diagnosis:
A personalised management plan is developed
Regular monitoring of growth, development, and metabolic markers is initiated
Emergency protocols are prepared for illness or fasting
Nutritional therapy is started immediately
Ongoing education for parents, caregivers, and schools ensures the child’s needs are met in all environments.
Conclusion | Diagnosis of Glutaric Aciduria Type 1
The diagnosis of glutaric aciduria type 1 is most effective when made early through newborn screening. Furthermore, followed by confirmatory biochemical and genetic testing. Timely and accurate diagnosis of glutaric aciduria type 1 enables intervention before the onset of serious neurological symptoms, improving outcomes and quality of life. With proper diagnosis, families can be empowered to manage the condition confidently and proactively.
