How is Glutaryl-CoA dehydrogenase deficiency / Glutaric aciduria type 1 diagnosed?

Diagnosis of Glutaryl-CoA dehydrogenase deficiency / Glutaric aciduria type 1

Glutaryl-CoA dehydrogenase deficiency, also known as Glutaric aciduria type 1 (GA1), is a rare genetic disorder that affects the metabolism of certain amino acids. It is caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase, which leads to the accumulation of toxic substances in the body.

Diagnosing GA1 can be challenging as its symptoms can vary widely and may not be apparent at birth. However, early detection and diagnosis are crucial for the management and treatment of the condition.

1. Newborn Screening: In many countries, GA1 is included in the newborn screening panel, which involves testing a small blood sample taken from the baby's heel shortly after birth. The screening measures the levels of certain metabolites, including glutaric acid, in the blood. Elevated levels of glutaric acid can indicate a potential GA1 diagnosis.

2. Clinical Evaluation: If GA1 is suspected based on newborn screening results or clinical symptoms, a comprehensive evaluation by a healthcare professional is necessary. The evaluation may include:

• Medical History: The doctor will review the child's medical history, including any symptoms or developmental delays.


• Physical Examination: A thorough physical examination may be conducted to assess any physical abnormalities or neurological signs.


• Neurological Assessment: GA1 can affect the central nervous system, so a neurological assessment is crucial. This may involve evaluating muscle tone, reflexes, and motor skills.

3. Laboratory Tests: Various laboratory tests can aid in the diagnosis of GA1:

• Urine Organic Acid Analysis: A urine sample is collected and analyzed to measure the levels of organic acids, including glutaric acid. Elevated levels of glutaric acid can indicate GA1.


• Plasma Amino Acid Analysis: Blood samples are taken to measure the levels of amino acids. GA1 can cause imbalances in certain amino acids, such as glutamine, lysine, and tryptophan.


• Genetic Testing: Genetic testing can confirm the diagnosis of GA1 by identifying mutations in the GCDH gene, which is responsible for producing the glutaryl-CoA dehydrogenase enzyme.

4. Imaging Studies: Imaging studies, such as magnetic resonance imaging (MRI), may be performed to assess the brain for any structural abnormalities or damage.

5. Family History: GA1 is an autosomal recessive disorder, meaning both parents must carry a mutated gene for their child to be affected. Therefore, obtaining a detailed family history can help identify other family members who may be at risk of carrying the gene.

Early diagnosis of GA1 is crucial to prevent or minimize the development of neurological complications. Once diagnosed, treatment can involve a strict low-protein diet, special formulas, and the supplementation of certain vitamins and cofactors. Regular monitoring and follow-up with healthcare professionals are essential to manage the condition effectively.