AI Article Synopsis
- A case of MCT8 deficiency, a rare genetic disorder linked to the SLC16A2 gene, showcases how it causes severe neurodevelopmental issues in males but can also affect females, as seen in this girl's condition.
- The 17-year-old girl exhibited significant developmental delays, epilepsy, and hormonal imbalances, leading to her diagnosis during an evaluation for primary ovarian insufficiency.
- Genetic analysis revealed a balanced translocation that disrupted the SLC16A2 gene, confirming that skewed X-chromosome inactivation can make females symptomatic in cases of MCT8 deficiency.
Article Abstract
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.
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| http://dx.doi.org/10.1515/jpem-2023-0070 | DOI Listing |
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