Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment

Abstract

Defective thyroid hormone transport due to deficiency in thyroid hormone transporter monocarboxylate transporter 8 (MCT8) results in severe neurodevelopmental delay due to cerebral hypothyroidism and in clinical negative sequelae following a chronic thyrotoxic state in peripheral tissues. The life expectancy of patients with MCT8 deficiency is severely impaired. Increased mortality is associated with lack of head control and being underweight at young age. Treatment options are available to alleviate the thyrotoxic state; particularly, treatment with the thyroid hormone analogue triiodothyroacetic acid seems a promising therapy. This review provides an overview of key clinical features and treatment options available and under development for this rare disorder.

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome

“…Key hallmarks of the AHDS are decreased thyroid hormone levels in the brain with elevated (T3) or decreased level (T4) in the periphery. These endocrine abnormalities manifest in severe cognitive and motor impairments, hypotonia, muscle hypoplasia, spasticity and severe intellectual disability [ 27 ]. Consistent with a chronic state of cerebral hypothyroidism and peripheral thyrotoxicity, patients with AHDS show increased mortality and reduced life expectancy [ 27 ].…”

“…These endocrine abnormalities manifest in severe cognitive and motor impairments, hypotonia, muscle hypoplasia, spasticity and severe intellectual disability [ 27 ]. Consistent with a chronic state of cerebral hypothyroidism and peripheral thyrotoxicity, patients with AHDS show increased mortality and reduced life expectancy [ 27 ]. While to this date there is no curative therapy, the development of pharmacotherapies to treat AHDS depends on the availability of a reliable model organism to assess treatment outcome.…”

AAV9-MCT8 delivery at juvenile stage ameliorates neurological and behavioral deficits in an Allan-Herndon-Dudley Syndrome mouse model

“…Being a rare disorder, AHDS is often misdiagnosed resulting in later identification of the disease. Moreover, there are currently about 300 diagnosed cases, which mostly involve older children 11,38 . Thus, it is important to develop therapeutics that are effective at juvenile ages.…”

Ganglioglioma with novel molecular features presenting in a child with Allan-Herndon-Dudley syndrome

“…10 11 Cerebral hypothyroidism is severely detrimental to neurodevelopment, 12 13 and clinical supplementation with thyroid hormone or its derivative has produced mixed results. [14][15][16][17] AHDS consequently exhibits a profound, heterogeneous clinical presentation featuring craniofacial deformity, intellectual disability and neurological abnormalities including seizures, developmental delay and impaired mobility. 18 19 We report the first case of a ganglioglioma-and perhaps the first CNS tumour overall-in a paediatric patient with AHDS.…”