Diagnosis of glutaric aciduria type I based on neuroradiological findings: when neonatal screening fails.

Background: Glutaric aciduria type I (GA-I) is an autosomal recessive disorder affecting the metabolism of lysine, hydroxylysine, and tryptophan. Patients present in the first age of life with an irreversible motor disorder, and neuroradiological imaging can suggest the presence of the condition. Biochemically, the disorder is characterized by elevated levels of glutaric and 3-hydroxy glutaric acid in the urine and glutarylcarnitine in the blood. This latter metabolite can be detected in dried blood spots, and the condition can therefore be included in some newborn screening programs.

Case presentation: We present the case of a patient affected by GA-I that was undetected by newborn screening in whom the diagnosis was clinically oriented at the age of nine months by acute neurological symptoms, represented by persistent tonic seizures, and by neuroimaging showing bilateral signal alterations in the basal ganglia. Biochemical data, including glutarylcarnitine in dried blood spots and urinary excretion of glutaric acid, were normal in the acute phase and during follow-up. Molecular analysis confirmed a diagnosis of GA-I, showing a homozygous M405V variant of the GCDH gene, which is common in African populations and associated with a low-excretor phenotype characteristic of the disorder.

Conclusions: In conclusion, although GA-I is included in neonatal screening programs, the biochemical markers in dried blood spots can be absent. Therefore, in patients of African origin, clinicians should maintain a high degree of vigilance in the presence of suggestive clinical and neuroradiological findings, even if biochemical parameters are normal.