Hypothyroidism due to biallelic variants in IYD: description of 4 families and a novel variant.

This article focuses on the clinical and genetic characterization of hypothyroidism caused by biallelic loss-of-function variants in the IYD gene, which encodes the iodotyrosine deiodinase enzyme responsible for intrathyroidal iodide recycling. The study describes eight patients from four consanguineous families, including one with a novel pathogenic IYD variant (c.791C>T [P264L]), who developed non-autoimmune goitrous hypothyroidism between 5 and 16 years of age. Findings indicate that overt hypothyroidism and goiter manifest when iodine intake is very low, while normal iodine intake maintains euthyroidism; elevated serum thyroglobulin levels precede clinical symptoms and may signal the need for iodine supplementation. Levothyroxine treatment generally reduced goiter size, but iodine status was closely correlated with thyroid function, underscoring the importance of adequate iodine intake in managing this rare genetic condition.