Moreno et al. (2002) described a patient with permanent and severe thyroid hormone deficiency and a complete iodide organification defect who was one of a group of 9 identified through a screening program for congenital hypothyroidism. At screening, ... Moreno et al. (2002) described a patient with permanent and severe thyroid hormone deficiency and a complete iodide organification defect who was one of a group of 9 identified through a screening program for congenital hypothyroidism. At screening, this patient had thyroxine levels below the limit of detection and very high thyrotropin levels. The other 8 patients studied had mild transient congenital hypothyroidism and a partial iodide organification defect.
Moreno et al. (2002) analyzed DNA of 9 patients with idiopathic congenital hypothyroidism and an iodide organification defect for mutations in the genes for DUOX1 (606758) and DUOX2. In a patient with permanent and severe thyroid hormone deficiency ... Moreno et al. (2002) analyzed DNA of 9 patients with idiopathic congenital hypothyroidism and an iodide organification defect for mutations in the genes for DUOX1 (606758) and DUOX2. In a patient with permanent and severe thyroid hormone deficiency and a complete iodide organification defect, Moreno et al. (2002) detected homozygosity for a nonsense mutation (606759.0001) in the DUOX2 gene that eliminated all functional domains of the protein. Three of the 8 patients with mild transient congenital hypothyroidism and a partial iodide organification defect had heterozygous mutations in the DUOX2 gene that prematurely truncated the protein, thus abolishing its functional domains. Moreno et al. (2002) observed that monoallelic mutations, associated with mild, transient hypothyroidism, resulted in insufficient thyroid production of hydrogen peroxide, which prevented the synthesis of sufficiently large quantities of thyroid hormones required at the beginning of life. In 2 brothers with congenital hypothyroidism, Vigone et al. (2005) identified compound heterozygosity for mutations in the DUOX2 gene (606759.0003 and 606759.0004). The euthyroid parents were heterozygous for the mutations. The brothers were reevaluated at age 4 after 1 month of levothyroxine withdrawal, at which time they had mildly increased serum thyroid-stimulating hormone levels and normal free thyroid hormone levels. They were at the 75th centile in both height and weight and had adequate cognitive development (IQs of 103 and 112, respectively) and normal hearing. Due to persistent hyperthyrotropinemia, levothyroxine was restarted in both children. Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder.