Magnetic Resonance Imaging Findings During Encephalopathic Crisis in Glutaric Aciduria Type 1: Expanding the Radiologic Phenotype

A 6-month-old boy, born to nonconsanguineous parents, with an uneventful perinatal period and motor developmental delay, presented with acute-onset seizures and encephalopathy following a febrile illness. Examination showed macrocephaly (>97^th centile), hypotonia, and apathetic facies. Ophthalmologic examination revealed a normal anterior chamber. Fundoscopy showed mild pallor of the optic disc, altered fovea with features of macular dystrophy, and normal vessels [Supplementary File Figure 1a ^{(1.2MB, tif)} ]. Magnetic resonance imaging (MRI) of the brain showed poor opercularization of the bilateral sylvian fissures, with subdural collections along the bilateral frontotemporoparietal convexities, suggesting the possibility of glutaric aciduria type 1 [Figure 1].[1] Symmetric diffusion restriction was noted in the basal ganglia, frontal white matter, optic chiasm, and central tegmental tracts [Figure 2 and Supplementary File Figure 1b ^{(1.2MB, tif)} ].[2]

Figure 1.

(a) Axial T2-weighted sequence showing a batwing appearance of the sylvian fissures (arrows). (b) Axial T2-weighted FLAIR sequence showing subdural collections along the frontotemporoparietal convexities (arrows). FLAIR: Fluid-attenuated inversion recovery

Figure 2.

Axial DWI sequence (b1000) showing (a) symmetric hyperintense signals in the basal ganglia (solid arrows) and frontal white matter (dotted arrows); (b) the optic chiasm (arrow); and (c) the central tegmental tracts (arrow). DWI: Diffusion-weighted imaging

The differentials for restricted diffusion in the basal ganglia in the toddler age group are broad and include metabolic, toxic, ischemic, and infectious causes. Energy-dependent metabolic disorders, such as mitochondrial disease (especially the Leigh phenotype) and organic acidemias, as well as acquired injuries like hypoxic-ischemic encephalopathy and carbon monoxide poisoning, are other common etiologies. Bilateral sylvian fissure widening suggests underdevelopment of the opercular cortex. Congenital bilateral perisylvian syndrome and its milder phenotype, Worster–Drought syndrome, are common differentials apart from glutaric aciduria. Subdural collections in late infancy are commonly seen in nonaccidental head trauma (shaken baby syndrome), following ventriculoperitoneal shunts, and in cerebral atrophy after ischemic injury. Spongiform myelinopathy has been postulated as the pathomechanism underlying cytotoxic edema and diffusion restriction of the optic chiasm.

Urine gas chromatography-mass spectrometry (GC–MS) showed elevated 3-hydroxyglutaric acid (791.5 mmol/mol), glutaric acid-2 (7560.03 mmol/mol), and glutaconic acid-2 (81.83 mmol/mol); transcranial magnetic stimulation (TMS) showed increased levels of glutarylcarnitine (0.57 μmol/L) and 3-hydroxyhexanoylcarnitine metabolites, with a decreased level of free carnitine (5.22 μmol/L), confirming glutaric aciduria type 1.[3] This case demonstrates unique extra-striatal MRI abnormalities during an encephalopathic crisis in glutaric aciduria type 1, which are otherwise rarely reported.[4]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Supplementary Figure 1

(a) Funduscopy: Clear media, background tessellation, mild pallor of the optic disc, altered fovea, normal vessels. (b) Reconstructed coronal image of the DWI sequence showing hyperintensities in the basal ganglia (arrows) and the optic chiasm (dotted arrow). DWI: Diffusion weighted imaging

Funding Statement

Nil.