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Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?
Pieter Vancamp1, Barbara A Demeneix1, Sylvie Remaud1
1UMR 7221 Molecular Physiology and Adaptation, Centre National de le Recherche Scientifique-Muséum National d'Histoire Naturelle, Paris, France.
Frontiers in Endocrinology
|June 2, 2020
Summary
Monocarboxylate transporter 8 (MCT8) deficiency, or Allan-Herndon-Dudley Syndrome (AHDS), impairs thyroid hormone transport, leading to intellectual disability. Research highlights conflicting interpretations of myelination defects and calls for new therapeutic strategies.
Area of Science:
- Neuroscience
- Genetics
- Endocrinology
Background:
- Allan-Herndon-Dudley Syndrome (AHDS) is an X-linked disorder caused by mutations in the SLC16A2 gene, affecting the Monocarboxylate transporter 8 (MCT8).
- MCT8 deficiency impairs thyroid hormone transport, crucial for brain development, leading to psychomotor disability and intellectual disability.
- While neuronal pathology is recognized, the glial component and its role in white matter (WM) abnormalities, particularly myelination, remain inadequately investigated.
Purpose of the Study:
- To clarify the conflicting interpretations regarding myelin status in AHDS patients.
- To investigate the pathophysiological mechanisms underlying myelination defects in MCT8 deficiency.
- To identify knowledge gaps in the spatial and temporal progression of myelination in AHDS to inform therapeutic strategies.
Main Methods:
- Analysis of myelin status in AHDS patients using various methodologies, including individual case studies, post-mortem analyses, and high-resolution MRI.
- Linking clinical findings in patients with data from animal models of MCT8 deficiency.
- Review of thyroid hormone signaling pathways and their role in oligodendrocyte generation and myelinogenesis.
Main Results:
- Conflicting reports on myelination in AHDS: some suggest delayed but restored myelination, while others indicate permanent hypomyelination and WM abnormalities.
- Methodological differences in assessing WM microstructure contribute to varying interpretations of myelin status.
- The precise relationship between specific MCT8 mutations and the severity of myelin deficiency remains unclear.
Conclusions:
- MCT8 deficiency leads to complex white matter abnormalities, with myelination defects being a key hallmark.
- Inconsistent terminology and misdiagnosis highlight the need for clearer understanding and diagnostic criteria for AHDS.
- Further research into the spatiotemporal progression of myelination and testing of MCT8-independent therapies are crucial for developing effective treatments.
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