A 12-month-old male patient of Yemeni descent presented to the emergency room after 48 hours of fever, poor oral intake, and impaired movements. He was reportedly in his normal state of health until 2 days earlier, when he developed a fever, cough, and rhinorrhea. Six hours prior to presentation, he was noted to appear increasingly more lethargic and refused to bear weight or reach for things. His parents said that he “felt really stiff” and seemed “really tired despite waking up from his nap.”

History was notable as follows: The child was born in Yemen to consanguineous parents and did not receive newborn screening. The parents reported he was born at full term and was noted to have a “large head” without a history of neurodevelopmental delays. He was noted to avoid eating meat despite the rest of his family doing so. There was a reported family history of multiple cousins dying of “meningitis” in early infancy. His parents had recently been battling upper respiratory infections as well. He was up to date on vaccinations. He was not on any medications and had no prior medical history or known allergies. On general examination, he was febrile, appeared mildly dehydrated, and was grossly macrocephalic. He had a reduced level of consciousness and was minimally responsive to pain with IV insertion. He was observed to have spontaneous dystonic posturing of his arms and legs. Plantar response was upgoing bilaterally. Initial viral screen in the emergency room was positive for influenza B despite a reported history of influenza vaccination.

Brain MRI demonstrated widening of Sylvian fissures and symmetrical T2 hyperintensity of the basal ganglia ( Fig. 33.1 ). Blood, urine, and CSF cultures were negative for bacteria. White blood count, including neutrophil count and lymphocyte count, was appropriately elevated. Biochemical testing demonstrated elevated glutaric acid and 3-hydroxyglutaric acid on urine organic acids. Confirmatory genetic testing demonstrated a homozygous pathogenic variant in the GCDH gene.

Glutaric aciduria type 1. Brain MRI, axial T2 shows widened, square-shaped Sylvian fissures ( arrows ) with bilateral hyperintensity and volume loss of posterior putamina and globi pallidi ( arrowheads ).

The history of acute encephalopathy in an infant raises concern for infection (e.g., encephalitis, meningitis, sepsis), toxic ingestion, possible nonaccidental injury, and inborn errors of metabolism (IEMs).