Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development
Ferdy S van Geest1, Nilhan Gunhanlar1, Stefan Groeneweg1
1Academic Center For Thyroid Disease, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
Frontiers in Endocrinology
|September 20, 2021
Summary
Genetic defects in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) cause severe intellectual disability and peripheral thyrotoxicosis. Triiodothyroacetic acid shows promise for treating peripheral symptoms, with neurocognitive effects under investigation.
Area of Science:
- Endocrinology
- Neuroscience
- Genetics
Background:
- Monocarboxylate transporter 8 (MCT8) deficiency arises from genetic defects in the MCT8 gene.
- This disorder impairs thyroid hormone transport, leading to severe neurodevelopmental deficits and peripheral thyrotoxicosis.
- MCT8 is vital for thyroid hormone transport across the blood-brain barrier, impacting cerebral signaling.
Purpose of the Study:
- To review the physiological role of MCT8.
- To outline the pathophysiology and clinical characteristics of MCT8 deficiency.
- To discuss current and emerging treatment options for MCT8 deficiency.
Main Methods:
- This review synthesizes current knowledge on MCT8 deficiency.
- It examines the molecular mechanisms, clinical presentations, and therapeutic strategies.
- Literature search and analysis of existing studies on MCT8 and related thyroid hormone transport.
Main Results:
- MCT8 deficiency causes profound intellectual and motor disabilities due to impaired brain thyroid hormone signaling.
- Patients exhibit peripheral thyrotoxicosis from elevated serum T3 levels.
- Poor head control and underweight status correlate with increased mortality.
Conclusions:
- Triiodothyroacetic acid effectively treats peripheral thyrotoxicosis in MCT8 deficiency.
- Further research is needed to evaluate its impact on neurocognitive outcomes.
- Developing novel therapies is crucial for improving patient outcomes and life expectancy.
Keywords:
Allan-Herndon-Dudley syndrome (AHDS)MCT8 deficiencymonocarboxylate transporter 8thyroid hormone signalingthyroid hormone transportMore Related Videos
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