Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations

Iodotyrosine deiodinase is a thyroidal enzyme that deiodinates mono- and di-iodotyrosines (MIT, DIT) and recycles iodine, a scarce element in the environment, for the efficient synthesis of thyroid hormone. Failure of this enzyme leads to hypothyroidism, goiter and mental retardation, a clinical phenotype yet described in the 1950s, whose diagnostic hallmark is the elevation of iodotyrosines in serum and urine.DEHAL1, the gene responsible for this activity, was recently isolated and the molecular basis for the iodotyrosine deiodinase deficiency (ITDD) unraveled. The current clinical picture of mutations in DEHAL1 mostly recapitulates the “classical” phenotype of ITDD, including the psychomotor deficits. This is probably due to the lack of expression of the disease at the beginning of life, which causes ITDD being undetected in current screening programs for congenital hypothyroidism. This worrying feature calls for efforts to improve the preclinical detection of iodotyrosine deiodinase deficiency in the neonatal time.