Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development
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 p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.723750/full |
| _version_ | 1818606809745719296 |
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| author | Ferdy S. van Geest Nilhan Gunhanlar Stefan Groeneweg W. Edward Visser |
| author_facet | Ferdy S. van Geest Nilhan Gunhanlar Stefan Groeneweg W. Edward Visser |
| author_sort | Ferdy S. van Geest |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T14:16:46Z |
| format | Article |
| id | doaj.art-94702acd654e447198faf2d8dfecce1e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-16T14:16:46Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-94702acd654e447198faf2d8dfecce1e2022-12-21T22:28:35ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-09-011210.3389/fendo.2021.723750723750Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy DevelopmentFerdy S. van GeestNilhan GunhanlarStefan GroenewegW. Edward VisserGenetic 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.723750/fullMCT8 deficiencymonocarboxylate transporter 8Allan-Herndon-Dudley syndrome (AHDS)thyroid hormone transportthyroid hormone signaling |
| spellingShingle | Ferdy S. van Geest Nilhan Gunhanlar Stefan Groeneweg W. Edward Visser Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development Frontiers in Endocrinology MCT8 deficiency monocarboxylate transporter 8 Allan-Herndon-Dudley syndrome (AHDS) thyroid hormone transport thyroid hormone signaling |
| title | Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development |
| title_full | Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development |
| title_fullStr | Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development |
| title_full_unstemmed | Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development |
| title_short | Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development |
| title_sort | monocarboxylate transporter 8 deficiency from pathophysiological understanding to therapy development |
| topic | MCT8 deficiency monocarboxylate transporter 8 Allan-Herndon-Dudley syndrome (AHDS) thyroid hormone transport thyroid hormone signaling |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.723750/full |
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