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Genetic defects in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in MCT8 deficiency. This disorder is characterized by a combination of severe intellectual and motor disability, caused by decreased cerebral thyroid hormone signalling, and a chronic thyrotoxic state in peripheral tissues, caused by exposure to elevated serum T3 concentrations. In particular, MCT8 plays a crucial role in the transport of thyroid hormone across the blood-brain-barrier. The life expectancy of patients with MCT8 deficiency is strongly impaired. Absence of head control and being underweight at a young age, which are considered proxies of the severity of the neurocognitive and peripheral phenotype, respectively, are associated with higher mortality rate. The thyroid hormone analogue triiodothyroacetic acid is able to effectively and safely ameliorate the peripheral thyrotoxicosis; its effect on the neurocognitive phenotype is currently under investigation. Other possible therapies are at a pre-clinical stage. This review provides an overview of the current understanding of the physiological role of MCT8 and the pathophysiology, key clinical characteristics and developing treatment options for MCT8 deficiency., Competing Interests: The Erasmus Medical Centre (Rotterdam, Netherlands), which employs FSvG, NG, SG, and WEV receives royalties from Rare Thyroid Therapeutics (the manufacturer of Triac), dependent on commercialisation. None of the authors will benefit personally from any royalties. None of the authors have personal disclosures relevant to this work., (Copyright © 2021 van Geest, Gunhanlar, Groeneweg and Visser.)

Purpose: The aim of the study was to assess the predictive value of preoperatively assessed diffusion kurtosis imaging (DKI) metrics as prognostic factors in the 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups., Material and Methods: Seventy-seven patients with histopathologically confirmed treatment-naïve glioma were retrospectively assessed between 08/2013 and 10/2017 using mean kurtosis (MK) and mean diffusivity (MD) histogram parameters from DKI, overall and progression-free survival, and relevant prognostic molecular data (isocitrate dehydrogenase, [IDH]; alpha-thalassemia/mental retardation syndrome X-linked, [ATRX]; chromosome 1p/19q loss of heterozygosity). Receiver operating characteristic (ROC) analysis was performed on metric variables to determine the optimal cutoff-values. The Kaplan-Meier method was used to assess univariate survival data. A multivariate Cox proportional hazards model was performed on significant results from the univariate analysis., Results: There were significant differences in overall and progression-free survival between patient age (p = 0.001), resection statuses (p = 0.002), WHO glioma grades (p < 0.0001), and integrated molecular profiles (p < 0.0001). Survival was significantly better in patients with lower MK and higher MD values globally (p = 0.009), in gliomas without chromosome 1p/19q LOH (p < 0.0001), and those with retained ATRX expression (p = 0.008)., Conclusions: Patient age and MK from DKI from DKI are relevant factors for preoperatively predicting overall and progression-free survival. Regarding the molecular subgroups, they seem to be predictive in gliomas with ATRX retention, representing a feature of IDH wild-type gliomas., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The BCAP31 gene is located between SLC6A8, associated with X-linked creatine transporter deficiency, and ABCD1, associated with X-linked adrenoleukodystrophy. Recently, loss-of-function mutations in BCAP31 were reported in association with severe developmental delay, deafness and dystonia. We characterized the break points in eight patients with deletions of SLC6A8, BCAP31 and/or ABCD1 and studied the genotype-phenotype correlations. The phenotype in patients with contiguous gene deletions involving BCAP31 overlaps with the phenotype of isolated BCAP31 deficiency. Only deletions involving both BCAP31 and ABCD1 were associated with hepatic cholestasis and death before 1 year, which might be explained by a synergistic effect. Remarkably, a patient with an isolated deletion at the 3'-end of SLC6A8 had a similar severe phenotype as seen in BCAP31 deficiency but without deafness. This might be caused by the disturbance of a regulatory element between SLC6A8 and BCAP31., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Normal function of the thyroid gland is the cornerstone of a child's mental development and physical growth. We describe a Finnish family, in which the diagnosis of three brothers became clear after investigations that lasted for more than 30 years. Two of the sons have already died. DNA analysis of the third one, a 16-year-old boy, revealed in exome sequencing of the complete X chromosome a mutation in the SLC16A2 gene, i.e. MCT8, coding for a thyroid hormone transport protein. Allan-Herndon-Dudley syndrome was thus shown to be the cause of multiple disabilities.