title: Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency: Implications for Diagnosis and Therapies.
abstract: 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.
authors.affiliation: Department of Radiology and Radiological Sciences, Medical University of South Carolina, Charleston, SC, USA matheus@musc.edu.
authors.forename: Maria Gisele
authors.initials: MG
authors.lastname: Matheus
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Lehman
authors.affiliation: Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bonilha
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA Department of Neurology, Medical University of South Carolina, Charleston, SC, USA Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Holden
mesh_terms: D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D004421:Dystonia / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D009123:Muscle Hypotonia / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D009133:Muscular Atrophy / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D010641:Phenotype
keywords: diffusion tensor imaging; dystonia; magnetic resonance imaging; monocarboxylate transporter 8 deficiency; white matter tract