MCT8 - AHDS Foundation

Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency: Implications for Diagnosis and Therapies

Maria Gisele Matheus, MD, Rebecca K. Lehman, MD, Leonardo Bonilha, MD, PhD, and Kenton R. Holden, MD

X-linked monocarboxylate transporter 8 (MCT8) deficiency results from a loss-of-function mutation in the monocarboxylate
transporter 8 gene, located on chromosome Xq13.2 (Allan-Herndon-Dudley syndrome). Affected boys present early in life with
neurodevelopment delays but have pleasant dispositions and commonly have elevated serum triiodothyronine. They also have
marked axial hypotonia and quadriparesis but surprisingly little spasticity early in their disease course. They do, however, have
subtle involuntary movements, most often dystonia. The combination of hypotonia and dystonia presents a neurorehabilitation
challenge and explains why spasticity-directed therapies have commonly produced suboptimal responses. Our aim was to better
define the spectrum of motor disability and to elucidate the neuroanatomic basis of the motor impairments seen in MCT8 deficiency using clinical observation and brain magnetic resonance imaging (MRI) in a cohort of 6 affected pediatric patients. Our
findings identified potential imaging biomarkers and suggest that rehabilitation efforts targeting dystonia may be more beneficial
than those targeting spasticity in the prepubertal pediatric MCT8 deficiency population.