No abstract

Thyroid peroxidase (TPO) deficiency, caused by biallelic TPO mutations, is a well-established genetic form of congenital hypothyroidism (CH). More than 100 patients have been published, and the patients have been diagnosed mostly in the frame of newborn screening (NBS) programs. Correlation between clinical phenotypes and TPO activity remains unclear. Here, we report clinical and molecular findings of two unrelated TPO mutation-carrying mildly hypothyroid patients. The two patients were born at term after an uneventful pregnancy and delivery, and were NBS negative. They sought medical attention due to goiter at age 8 years. Evaluation of the thyroid showed mild elevation of serum TSH levels, normal or slightly low serum T levels, high serum T to T molar ratio, high serum thyroglobulin levels, and high thyroidal I uptake. We performed next-generation sequencing-based genetic screening, and found that one patient was compound heterozygous for two novel TPO mutations (p.Asp224del; c.820-2A>G), and the other was homozygous for a previously known mutation (p.Trp527Cys). In vitro functional analyses using HEK293 cells showed that the two amino acid-altering mutations (p.Asp224del and p.Trp527Cys) caused partial loss of the enzymatic activity. In conclusion, we report that TPO mutations with residual activity are associated with mild TPO deficiency, which is clinically characterized by marked goiter, mild TSH elevation, high serum T to T molar ratio, and high serum thyroglobulin levels. Our findings illuminate the hitherto under-recognized correlation between clinical phenotypes and residual enzymatic activity among patients with TPO deficiency.

Background It is important to identify the pathological characteristics of cerebral circulation and oxygen metabolism at the bedside in children with congenital heart disease (CHD) to prevent neurodevelopmental impairments. The brain regional oxygen saturation index (rSO2) can be easily obtained at the bedside with near‐infrared spectroscopy and has been widely used in the management of children with CHD in recent years. Methods To determine if the rSO2 before or after CHD surgery is a good predictor of cerebral oxygen metabolism, we investigated the impact of different clinical variables on the correlation between rSO2 and reference values under steady ratios of hemoglobin oxygen saturation in the internal jugular vein (SjvO2) or femoral artery (SaO2) (0.75:0.25, 0.66:0.34, and 0.50:0.50) in 186 children with CHD undergoing cardiac catheterization. Results In three patient groups—double ventricles before surgery, double ventricles after surgery, and single ventricle before surgery—there were significant relationships between rSO2 and the reference values of SO2 under all three steady ratios of SjvO2 and SaO2. No relationship with the reference values was found for the single ventricle after surgery group. Conclusions Regional oxygen saturation index is useful for assessing cerebral oxygenation in children with CHD, but knowledge of the underlying cardiac pathology in CHD, especially in the case of a single ventricle after surgery, is important for the correct interpretation of rSO2 measurements obtained using near‐infrared spectroscopy.

A case of pediatric atrial fibrillation ablation resulting in unilateral pulmonary vein occlusion during longterm follow-up, HeartRhythm Case Reports (2022), doi: https://doi.org/10.1016/j.hrcr.2021.12.017. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.