Parent Perspectives on Complex Needs in Patients With MCT8 Deficiency: An International, Prospective, Registry Study

Geest, Ferdy S van; Groeneweg, Stefan; Popa, V.; Stals, Milou A.M.; Visser, Willy

doi:10.1210/clinem/dgad412

Cited by 4 publications

(1 citation statement)

References 16 publications

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“…The treatment of patients with MCT8 deficiency remains challenging ( 20 ), and daily care poses a heavy burden on caregivers ( 21 ). Current options can only ameliorate thyroid test abnormalities associated with hypermetabolism without improvement of the severe neurologic defects.…”

Section: Introductionmentioning

confidence: 99%

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Salas-Lucia,

Escamilla,

Bianco

et al. 2024

JCI Insight

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Patients with mutations in the thyroid hormone (TH) cell transporter monocarboxylate transporter 8 ( MCT8 ) gene develop severe neuropsychomotor retardation known as Allan-Herndon-Dudley syndrome (AHDS). It is assumed that this is caused by a reduction in TH signaling in the developing brain during both intrauterine and postnatal developmental stages, and treatment remains understandably challenging. Given species differences in brain TH transporters and the limitations of studies in mice, we generated cerebral organoids (COs) using human induced pluripotent stem cells (iPSCs) from MCT8-deficient patients. MCT8-deficient COs exhibited (i) altered early neurodevelopment, resulting in smaller neural rosettes with thinner cortical units, (ii) impaired triiodothyronine (T3) transport in developing neural cells, as assessed through deiodinase-3–mediated T3 catabolism, (iii) reduced expression of genes involved in cerebral cortex development, and (iv) reduced T3 inducibility of TH-regulated genes. In contrast, the TH analogs 3,5-diiodothyropropionic acid and 3,3′,5-triiodothyroacetic acid triggered normal responses (induction/repression of T3-responsive genes) in MCT8-deficient COs, constituting proof of concept that lack of T3 transport underlies the pathophysiology of AHDS and demonstrating the clinical potential for TH analogs to be used in treating patients with AHDS. MCT8-deficient COs represent a species-specific relevant preclinical model that can be utilized to screen drugs with potential benefits as personalized therapeutics for patients with AHDS.

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Section: Introductionmentioning

confidence: 99%

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Salas-Lucia,

Escamilla,

Bianco

et al. 2024

JCI Insight

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Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients

Weiss,

Lemos,

Dumitrescu

et al. 2024

Thyroid®

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Unmet patient needs in monocarboxylate transporter 8 (MCT8) deficiency: a review

Bauer,

Auble,

Clark

et al. 2024

Front. Pediatr.

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Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the SLC16A2 gene and resulting from dysfunctional thyroid hormone transport. This disorder is characterized by profound neurodevelopmental delay and motor disability due to a lack of thyroid hormone in the brain, and coexisting endocrinological symptoms, due to chronic thyrotoxicosis, resulting from elevated thyroid hormone outside the central nervous system (CNS). In February 2024, we reviewed the published literature to identify relevant articles reporting on the current unmet needs of patients with MCT8 deficiency. There are several main challenges in the diagnosis and treatment of MCT8 deficiency, with decreased awareness and recognition of MCT8 deficiency among healthcare professionals (HCPs) associated with misdiagnosis and delays in diagnosis. Diagnostic delay may also be attributed to other factors, including the complex symptomology of MCT8 deficiency only becoming apparent several months after birth and pathognomonic serum triiodothyronine (T3) testing not being routinely performed. For patients with MCT8 deficiency, multidisciplinary team care is vital to optimize the support provided to patients and their caregivers. Although there are currently no approved treatments specifically for MCT8 deficiency, earlier identification and diagnosis of this disorder enables earlier access to supportive care and developing treatments focused on improving outcomes and quality of life for both patients and caregivers.

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Parent Perspectives on Complex Needs in Patients With MCT8 Deficiency: An International, Prospective, Registry Study

Cited by 4 publications

References 16 publications

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients

Unmet patient needs in monocarboxylate transporter 8 (MCT8) deficiency: a review

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