Towards the timely diagnosis of hypothyroidism caused by DEHAL1 gene defects

Abstract

DEHAL1 is the thyroidal enzyme that deiodinates mono- and diiodotyrosines (MIT, DIT) and recycles iodine, a scarce element in the environment, for the efficient synthesis of thyroid hormone. Failure of this enzyme leads to the iodotyrosine deiodinase deficiency (ITDD), a disease characterized by hypothyroidism, compressive goiter and variable mental retardation, whose diagnostic hallmark is the elevation of iodotyrosines in serum and urine. Mutations in the DEHAL1 gene were recently identified as the molecular basis for the iodotyrosine deiodinase deficiency. Patients harboring DEHAL1 defects so far described all belong to consanguineous families, and of psychomotor deficits were present in some affected individuals. 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 preclinical detection of iodotyrosine deiodinase deficiency in the neonatal time. Such a challenge poses questions of epidemiological (prevalence of disease), physiological (factors influencing biochemical expression of ITDD) and technical nature (development of optimal methodology for safe detection of preclinical ITDD), which will be addressed in this review.