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MCT8 deficiency

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Resumo:Background: MCT8 deficiency is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. It results in a state of T3 deprivation in the brain from early development, leading to severe psychomotor impairment and peripheral hyperthyroidism. Endocrinological symptoms develop over time due to thyrotoxicosis in tissues outside the brain. Methods: We present a case series of three male patients with genetically confirmed MCT8 deficiency. Results: All three patients exhibit profound psychomotor delay, with axial hypotonia, limb dystonia, and bradykinesia as consistent features. Genetic analysis identified three distinct SLC16A2 variants: two missense mutations (Thr353Pro and Ser232Phe) and one nonsense mutation (Glu144∗). The characteristic thyroid hormone profile of MCT8 deficiency – high T3, low T4 and reverse T3, and normal TSH – was observed in all cases. Conclusion: These cases illustrate the clinical and genetic heterogeneity of MCT8 deficiency, highlighting the key challenges faced by patients and their caregivers, and the need for earlier diagnosis.
Autores principais:Costa, Cristiana
Outros Autores:Painho, Teresa; Alcafache, Margarida; Marques-Matos, Cláudia; Fitas, Ana Laura
Assunto:AHDS Allan–Herndon–Dudley syndrome MCT8 MCT8 deficiency SLC16A2 Thyroid hormone Endocrinology, Diabetes and Metabolism Endocrinology SDG 3 - Good Health and Well-being
Ano:2026
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL
Descrição
Resumo:Background: MCT8 deficiency is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. It results in a state of T3 deprivation in the brain from early development, leading to severe psychomotor impairment and peripheral hyperthyroidism. Endocrinological symptoms develop over time due to thyrotoxicosis in tissues outside the brain. Methods: We present a case series of three male patients with genetically confirmed MCT8 deficiency. Results: All three patients exhibit profound psychomotor delay, with axial hypotonia, limb dystonia, and bradykinesia as consistent features. Genetic analysis identified three distinct SLC16A2 variants: two missense mutations (Thr353Pro and Ser232Phe) and one nonsense mutation (Glu144∗). The characteristic thyroid hormone profile of MCT8 deficiency – high T3, low T4 and reverse T3, and normal TSH – was observed in all cases. Conclusion: These cases illustrate the clinical and genetic heterogeneity of MCT8 deficiency, highlighting the key challenges faced by patients and their caregivers, and the need for earlier diagnosis.