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Multicenter Study
. 2024 Dec 19;184(1):92.
doi: 10.1007/s00431-024-05931-7.

Clinical and genetic characteristics of patients with monocarboxylate transporter-8 deficiency: a multicentre retrospective study

Nurullah Çelik  1 , Korcan Demir  2 , Saime Ergen Dibeklioğlu  3 , Bumin Nuri Dündar  4 , Nihal Hatipoğlu  5 , Gül Yeşiltepe Mutlu  6 , Emrullah Arslan  7 , Didem Yıldırımçakar  8 , Atilla Çayır  9 , Bülent Hacıhamdioğlu  10 , Zümrüt Kocabey Sütçü  11 , Yağmur Ünsal  12 , Gülay Karagüzel  13
Affiliations
Multicenter Study

Clinical and genetic characteristics of patients with monocarboxylate transporter-8 deficiency: a multicentre retrospective study

Nurullah Çelik et al. Eur J Pediatr. .

Abstract

Allan-Herndon-Dudley syndrome is a neurodevelopmental disorder characterized by motor and intellectual disabilities. Despite its rarity, there has been a rise in interest due to ongoing research and emerging therapy suggestions. In this multicenter, retrospective, cross-sectional study, the genetic characteristics and clinical data of twenty-one cases of genetically confirmed MCT8 deficiency were evaluated. The median age at the diagnosis was 2.4 (1.29; 5.9) years, which ranged from 0.5 to 14.0 years. The median follow-up period was 2.34 years, ranging from four months to 7.9 years. In 21 patients, 17 different variants were detected in the SLC16A2 gene. Eleven of these variants (c.1456delC, c.439G > T, c.949C > A, c.1392dupC, c.1612C > T, c.407dup, c.781del, c.589C > A, c.712G > A, c.311 T > A, c.1461del) have not been previously reported. In this study, with the exception of three cases with fT3/fT4 ratios of 4.95, 3.58, and 4.52, all cases exhibited fT3/fT4 ratios higher than five (9.9 (7.9; 12.0)).

Conclusion: MCT8 deficiency is a rare and devastating disorder characterized by central hypothyroidism and peripheral thyrotoxicosis. The fT3/fT4 ratio can be used as a useful diagnostic indicator of MCT8 deficiency in males with mental and motor retardation. There is a need to raise clinicians' awareness of this potentially treatable condition with the emergence of new and promising treatments.

What is known: • Allan-Herndon-Dudley syndrome, also known as MCT8 deficiency is a rare and devastating disorder characterized by central hypothyroidism and peripheral thyrotoxicosis.

What is new: • In this study, seventeen different variants were detected in the SLC16A2 gene, eleven of which (c.1456delC; c.439G>T; c.949C>A; c.1392dupC; c.1612C>T; c.407dup; c.781del; c.589C>A; c.712G>A; c.311T>A; c.1461del) have not been reported before. • The fT3/fT4 ratio can be used as a useful diagnostic indicator of MCT8 deficiency in males with mental and motor retardation.

Keywords: Allan-Herndon-Dudley syndrome; MCT8 deficiency; Thyroid disease; Thyroid hormone transport.

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Conflict of interest statement

Declarations. Ethics approval: The Cumhuriyet University Ethics Committee approved the study protocol (2023–09/23). The principles of the Declaration of Helsinki and Good Clinical Practice for Biomedical Research were followed in conducting the study. Consent to participate: Written informed assent and consent were obtained from all participants and their parents before any procedures. Consent for publication: All authors consent to the publication of the manuscript in EJPE. Competing interests: The authors declare no competing interests.

References

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    1. van Geest FS, Gunhanlar N, Groeneweg S, Visser WE (2021) Monocarboxylate transporter 8 deficiency: from pathophysiological understanding to therapy development. Front Endocrinol 12:723750. https://doi.org/10.3389/fendo.2021.723750 - DOI
    1. Masnada S, Sarret C, Antonello CE et al (2022) Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome. Mol Genet Metab 135:109–113. https://doi.org/10.1016/j.ymgme.2021.12.003 - DOI - PubMed

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