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Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter

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Abstract

Thyroid hormones are known to be essential for growth, development, and metabolism. Recently, the monocarboxylate transporter 8 (MCT8) was identified as a thyroid hormone transporter, and MCT8 mutations have been associated with Allan-Herndon-Dudley syndrome, an X linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. Here we describe in detail the clinical and biochemical features and the response to thyroid hormone (L-thyroxine (LT4)) administration in a boy with an MCT8 mutation (c.1649delA) that truncates the protein in the twelfth transmembrane domain. It is of note that brain magnetic resonance imaging (MRI) revealed delayed myelination from infancy. Endocrine functions other than thyroid hormone regulation and metabolism were intact, resulting in normal hypothalamic/pituitary function tests. While LT4 administration suppressed thyrotropin (TSH) secretion, no significant changes in thyroid hormone values or clinical symptoms were observed. Conclusion: the characteristic thyroid hormone function tests and brain MRI findings may allow screening of high-risk populations for a better understanding of MCT8 pathophysiology.

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Abbreviations

AHDS:

Allan-Herndon-Dudley syndrome

CNS:

central nervous system

D1:

type I deiodinase

D2:

type II deiodinase

D3:

type III deiodinase

FSH:

follicle-stimulating hormone

fT3:

free T3

fT4:

free T4

GH:

growth hormone

IGF-I:

insulin-like growth factor-I

LH:

luteinizing hormone

LHRH:

luteinizing hormone-releasing hormone

LT4:

L-thyroxine

MCT8:

monocarboxylate transporter 8

MRI:

magnetic resonance imaging

MRS:

magnetic resonance spectroscopy

OATP:

organic acid transporting polypeptide

PRL:

prolactin

rT3:

reverse T3

T3:

triiodothyronine

T4:

thyroxine

TH:

thyroid hormone

TMD:

transmembrane domain

TRH:

thyrotropin-releasing hormone

TSH:

thyrotropin

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Acknowledgements

We thank the patient and the members of the family for their cooperation, Ms. Keiko Takeoka for the rT3 measurements, and Drs. Kuriko Kagitani-Shimono, Ken Araya, and Hisashi Tanaka for interpretation of the MRI images.

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Authors and Affiliations

  1. Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Noriyuki Namba, Yuri Etani, Taichi Kitaoka, Yasuko Nakamoto, Mariko Nakacho, Kazuhiko Bessho, Yoko Miyoshi, Sotaro Mushiake & Keiichi Ozono

  2. First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan

    Noriyuki Namba

  3. Research Center for Child Mental Development, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Ikuko Mohri & Masako Taniike

  4. Department of Pediatric Neurology, Morinomiya Hospital, Osaka, Japan

    Hiroshi Arai

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  1. Noriyuki Namba
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  2. Yuri Etani
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Correspondence to Keiichi Ozono.

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Namba, N., Etani, Y., Kitaoka, T. et al. Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter. Eur J Pediatr 167, 785–791 (2008). https://doi.org/10.1007/s00431-007-0589-6

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  • DOI: https://doi.org/10.1007/s00431-007-0589-6

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