Peer-reviewed article
Reverse T3 Level and T3 to Reverse T3 Ratio in Dried Blood Spot Samples at Birth May Facilitate Early Diagnosis of MCT8 Deficiency
Iwayama H, Kakita H, Iwasa M, Adachi S, Takano K et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This peer-reviewed study describes a laboratory method for diagnosing MCT8 deficiency (a rare genetic disorder affecting thyroid hormone transport) in newborns using dried blood spot samples. Researchers measured thyroid hormone levels in blood samples from healthy newborns and those with confirmed MCT8 deficiency, finding that certain hormone ratios differed significantly between groups. The study proposes using these hormone measurements as biomarkers for early diagnosis.
Key points
- MCT8 deficiency is an X-linked neurodevelopmental disorder caused by impaired thyroid hormone transporter function
- Reverse T3 levels were significantly lower in MCT8 cases (0.317 ng/mL) compared to healthy neonates (0.768 ng/mL)
- The T3/reverse T3 ratio showed clear separation between groups (3.04 in MCT8 vs. 1.01 in healthy) with no overlap
- T4 levels were lower in MCT8 cases (93.4 ng/mL vs. 156.7 ng/mL in healthy neonates)
- Study proposes dried blood spot hormone measurements as biomarkers for MCT8 diagnosis at birth
Limitations
This is a diagnostic accuracy study focused on laboratory methodology rather than child health outcomes or intervention effectiveness. The study does not evaluate whether early diagnosis leads to improved health outcomes, treatment options, or clinical benefits for affected children.
Abstract
Abstract Background: Monocarboxylate transporter 8 (MCT8) deficiency is an X- chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transporter across cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as inability of standard biomarkers of neonatal screening to make an early diagnosis. Here, we report for the first time the ability to identify MCT8 deficiency at birth using dried blood spot (DBS) samples. Methods: We measured T3, T4, and reverse T3 (rT3) levels in DBS samples obtained at birth in healthy neonates (n = 42) and neonates with genetically confirmed diagnosis of MCT8 deficiency (n = 6). T3, rT3 and T4 levels were measured in 8 mm diameter DBS samples using liquid chromatography-tandem mass spectrometry. Results: Mean ± SD level of T3 tended to be higher in the MCT8 group than that in healthy neonates (0.941 ± 0.183 ng/mL vs. 0.742 ± 0.195 ng/mL, p = 0.0525). More importantly rT3 level in the MCT8 group was significantly lower than that in healthy neonates (0.317 ± 0.065 ng/mL vs. 0.768 ± 0.196 ng/mL, p < 0.0001) and the T3/rT3 ratio in the MCT8 group was significantly higher (3.04 ± 0.67 vs. 1.01 ± 0.34, p < 0.0001) with no overlap of values. T4 was lower in the MCT8 group than in healthy babies (93.4 ± 22.4 ng/mL vs. 156.7 ± 35.9 ng/mL, p < 0.0005) and the T3/T4 ratio of the MCT8 deficient group was higher (0.0105 ± 0.0029 vs. 0.0051 ± 0.0010, p< 0.0001). Conclusion: rT3 and T3/rT3 ratio measured in the DBS obtained from neonates can serve as biomarkers for diagnosis of MCT8 deficiency at birth.