Sisters with Iodide Transport Defect Caused by a Mutation of the NIS Gene not Detected in Neonatal Mass Screening for Cretinism

We report sisters with congenital hypothyroidism due to iodide transport defect (ITD) not detected in neonatal mass screening for cretinism. The symptoms of hypothyroidism appeared at the age of about 3 years (elder sister) and 2 years (younger sister), respectively. Since a thyroidal function test revealed severe hypothyroidism, they have been treated with l-T4 and have remained euthyroid. Thyroidal 123I uptake and the saliva/serum radioactive iodide ratio confirmed ITD. Moreover, homozygous sodium/iodide (Na+/I-) symporter (NIS) gene mutation of G543E was seen as a result of genetic analysis. The reason why their hypothyroidism was not found in neonatal mass screening for cretinism was because Japanese ingest large amounts of iodine, and therefore the sisters could obtain enough iodine throuth breast feeding. As a result, we suspect that they could produce thyroid hormones to some extent without active iodine transport to their thyroid. It might be difficult for the neonatal mass screening for cretinism in Japan to discover hypothyroidism due to ITD.