OBJECTIVE: Glutaric aciduria type 1 (GA1) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase, leading to the accumulation of neurotoxic metabolites. Early diagnosis and treatment through newborn screening (NBS) can prevent severe neurological complications. However, the effectiveness of NBS for GA1, particularly in identifying low-excretor phenotypes, remains a subject of ongoing research. Our study aims to evaluate the effectiveness and limitations of NBS for GA1 over a 10-year period in northeast Italy.

MATERIALS AND METHODS: We analyzed data from 301,360 newborns screened between 1 January 2014 and 31 December 2024. Screening was performed using tandem mass spectrometry to measure glutarylcarnitine (C5DC) levels in dried blood spots. Positive cases underwent confirmatory testing and long-term follow-up.

RESULTS: Four patients were identified through NBS, with one false-positive and one false-negative case, resulting in a sensitivity of 80%. The mean age at diagnosis was 4.25 days. Despite early treatment, one patient (25%) experienced an acute encephalopathic crisis. Two out of three patients with available follow-up MRI showed white matter abnormalities. The false-negative case, homozygous for the p.Met405Val variant associated with a low-excretor phenotype, was diagnosed at nine months following an acute encephalopathic crisis.

CONCLUSIONS: NBS for GA1 allows early diagnosis and treatment, potentially improving neurological outcomes. However, challenges remain, including the occurrence of acute crises in treated patients and false-negative results in low-excretor phenotypes. Further research is needed to enhance screening sensitivity, particularly for low-excretor patients, and to optimize long-term management strategies.