Allan-Herndon-Dudley-Syndrome: Considerations about the Brain
                    Phenotype with Implications for Treatment Strategies

Heiko Krude; Heike Biebermann; Markus Schuelke; Timo D. Müller; Matthias Tschöp

doi:10.1055/a-1108-1456

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2020; 128(06/07): 414-422
DOI: 10.1055/a-1108-1456

Mini-Review

Allan-Herndon-Dudley-Syndrome: Considerations about the Brain Phenotype with Implications for Treatment Strategies

Heiko Krude

¹Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

,

Heike Biebermann

¹Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

,

Markus Schuelke

²Department of Neuropediatrics, Charité - Universitätsmedizin, Berlin, Germany

,

Timo D. Müller

³Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Centre Munich, Germany

⁵German Center for Diabetes Research (DZD), Neuherberg, Germany

⁶Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany

,

Matthias Tschöp

⁴Division of Metabolic Diseases, Technische Universität München, Munich, Germany

⁵German Center for Diabetes Research (DZD), Neuherberg, Germany

⁷Helmholtz Zentrum München, Germany

› Author Affiliations

Abstract

Despite its first description more than 75 years ago, effective treatment for “Allan-Herndon-Dudley-Syndrome (AHDS)”, an X-linked thyroid hormone transporter defect, is unavailable. Mutations in the SLC16A2 gene have been discovered to be causative for AHDS in 2004, but a comprehensive understanding of the function of the encoded protein, monocarboxylate transporter 8 (MCT8), is incomplete. Patients with AHDS suffer from neurodevelopmental delay, as well as extrapyramidal (dystonia, chorea, athetosis), pyramidal (spasticity), and cerebellar symptoms (ataxia). This suggests an affection of the pyramidal tracts, basal ganglia, and cerebellum, most likely already during fetal brain development. The function of other brain areas relevant for mood, behavior, and vigilance seems to be intact. An optimal treatment strategy should thus aim to deliver T3 to these relevant structures at the correct time points during development. A potential therapeutic strategy meeting these needs might be the delivery of T3 via a “Trojan horse mechanism” by which T3 is delivered into target cells by a thyroid hormone transporter independent T3 internalization.

Key words

Thyroid hormone transporter - Allan-Herndon-Dudley-Syndrome - pathophysiology

Full Text

References

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