OBJECTIVES: To report an unusual case of MCT8 deficiency (Allan-Herndon-Dudley syndrome), an X-linked condition caused by pathogenic variants in the SLC16A2 gene. Defective transport of thyroid hormones (THs) in this condition leads to severe neurodevelopmental impairment in males, while heterozygous females are usually asymptomatic or have mild TH abnormalities. CASE PRESENTATION: A girl with profound developmental delay, epilepsy, primary amenorrhea, elevated T3, low T4 and free T4 levels was diagnosed with MCT8-deficiency at age 17 years, during evaluation for primary ovarian insufficiency (POI). Cytogenetic analysis demonstrated balanced t(X;16)(q13.2;q12.1) translocation with a breakpoint disrupting SLC16A2. X-chromosome inactivation studies revealed a skewed inactivation of the normal X chromosome. CONCLUSIONS: MCT8-deficiency can manifest clinically and phenotypically in women with SLC16A2 aberrations when nonrandom X inactivation occurs, while lack of X chromosome integrity due to translocation can cause POI.
Mental Retardation, X-Linked , Primary Ovarian Insufficiency , Symporters , Male , Adolescent , Humans , Female , Mental Retardation, X-Linked/diagnosis , Mental Retardation, X-Linked/genetics , Mental Retardation, X-Linked/pathology , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Muscle Hypotonia/pathology , Muscular Atrophy/genetics , Muscular Atrophy/pathology , Delayed Diagnosis , Primary Ovarian Insufficiency/genetics , Monocarboxylic Acid Transporters/genetics , Translocation, Genetic , Symporters/genetics
