Glutaric aciduria type 1 as a mimicker of abusive head trauma in the era of newborn screening.

BACKGROUND

Glutaric aciduria type 1 (GA1) is a cerebral organic aciduria which untreated may lead to metabolic crisis and the development of a complex movement disorder. In addition to the motor phenotype, early natural history studies reported a high incidence of spontaneous subdural hemorrhage (SDH). This has led to the inclusion of GA1 in the differential diagnosis of isolated SDH concerning for abusive head trauma and the widespread use of costly biochemical and molecular testing in this population. Contemporary newborn screening (NBS) methods enable presymptomatic detection of GA1, although false negatives have been reported.

OBJECTIVE

In this single-center, 20-year retrospective review, we aimed to estimate the false negative rate of NBS for GA1 as well as the incidence of SDH as the presenting finding of GA1 in the post-NBS era.

PARTICIPANTS AND

SETTING

GA1 patients referred to the Texas Children's Hospital Metabolic Genetics Clinic from 2006 to 2025.

METHODS

Demographic data, NBS results, confirmatory biochemical and molecular studies, and neuroimaging reports were collected by retrospective chart review from all subjects when available.

RESULTS

All 20 GA1 patients referred to our center were ascertained by NBS including two patients with a "low-excretor" biochemical phenotype. Classic neuroradiographic findings were present in most patients. SDH was detected incidentally in a single patient who demonstrated additional characteristic neuroimaging findings.

CONCLUSIONS

Evaluation for GA1 in patients presenting with isolated SDH in the setting of a negative NBS is likely to be of limited value - especially in the absence of additional suggestive neuroradiological features.