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Emcitate (tiratricol)

MCT8 deficiency

Last updated
78 sources

Product information and disease descriptionPlace of product in therapyDisease description

Definition and etiology

4 evidence topics · 3 sources

Genetic etiology

“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.” (opens the source at this quote in a new tab)

Transporter function and loss-of-function mechanism

“Monocarboxylate transporter 8 (MCT8), the protein product of SLC16A2, is thought to play a crucial role in neuronal T3 uptake and in endothelial cells allowing partial entry of thyroid hormone through the blood-brain barrier. MCT8 deficiency results in an insufficient supply of T3 to nuclear T3 receptors.” (opens the source at this quote in a new tab)

“AHDS results from a loss of function of the MCT8 protein.” (opens the source at this quote in a new tab)

X-linked inheritance and recurrence risk

“AHDS is inherited in an X-linked manner. If the mother of a proband has an SLC16A2 pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the variant will be heterozygotes (carriers) and usually will not be clinically affected but may have minor thyroid test abnormalities.” (opens the source at this quote in a new tab)

“In a study of 24 affected individuals, 17 males had inherited the SLC16A2 pathogenic variant from their mother” (opens the source at this quote in a new tab)

“In a study of 24 affected individuals, seven had a de novo SLC16A2 pathogenic variant” (opens the source at this quote in a new tab)

Affected females with skewed X-chromosome inactivation

“MCT8 deficiency typically affects males due to its X-linked inheritance.” (opens the source at this quote in a new tab)

“Female patients with heterozygous pathogenic variants in SLC16A2 and skewed X-chromosome inactivation may present with variable neuro(psycho)logical, behavioral, and thyroid function test abnormalities.” (opens the source at this quote in a new tab)