INTRODUCTION: Loss-of-function mutations in the X-linked Monocarboxylate Transporter 8 (MCT8) gene result in thyroid hormone cell transporter deficiency. Affected children present with moderate-severe psychomotor disability, hypotonia, and dystonic movements.  Previously published brain MRI data suggests that these children have abnormal myelination in the absence of significant structural abnormalities.  In light of this data, we hypothesized that MCT8 deficiency affects the structural development of complex cortical networks— specifically regional subcortical connections—which can be assessed with MRI.

METHODS:  We reviewed fourteen brain MRIs from a multinational cohort of patients with MCT8 mutations (n=6), aged 8 months to 7 years. We obtained longitudinal conventional MRI data in 5 patients and longitudinal diffusion tensor imaging (DTI) in 2 patients to evaluate for regional micro-structural abnormalities.

RESULTS: T1- and T2-weighted imaging revealed delayed myelination at 8 months of age with slow improvement over time. By 3-to-5 years, the supratentorial white matter tracts showed patchy high T2 signal intensity that predominantly involved the peritrigonal regions and subcortical U-fibers.  DTI demonstrated multiple foci of reduced fractional anisotropy in the supratentorial white matter, suggesting the presence of subtle microstructural abnormalities.

CONCLUSION/DISCUSSION:  The white matter tract abnormalities seen on brain MRI likely reflect disruptions in cortical-subcortical connectivity.  These disruptions may explain certain aspects of the MCT8 deficiency phenotype and may guide future therapy selection.