The deiodinases are a group of membrane bound, NADPH-dependent, FAD-enhanced isoenzymes found in the thyroid, kidney, liver, and other organs. Patients with this defect lack the ability to deiodinate radiolabeled monoiodotyrosine (MIT) and diiodotyrosine (DIT). This results in ... The deiodinases are a group of membrane bound, NADPH-dependent, FAD-enhanced isoenzymes found in the thyroid, kidney, liver, and other organs. Patients with this defect lack the ability to deiodinate radiolabeled monoiodotyrosine (MIT) and diiodotyrosine (DIT). This results in continuous urinary loss of iodine and tyrosine from the body. Most of the earlier reported patients had severe congenital hypothyroidism. In a classic study, Hutchison and McGirr (1954, 1956) described this disorder in inbred, itinerant tinkers from western Scotland. Werdnig-Hoffman disease occurred also in this family, apparently as an independently inherited disorder. Kusakabe and Miyake (1963) described a mother and daughter plus 2 other unrelated individuals who showed defective peripheral iodotyrosine deiodination but essentially normal in vitro thyroidal activity. Kusakabe and Miyake (1964) reported 3 affected sisters, from a sibship of 7 born to healthy, first-cousin parents, whose thyroidal tissue lacked deiodinase activity, but whose peripheral tissues deiodinated radiolabeled MIT and DIT normally. The patients with these limited tissue defects had normal growth and development. Ismail-Beigi and Rahimifar (1977) found a mild variant of the defect in 3 children born to unaffected first cousins. Afink et al. (2008) described a highly consanguineous Belgian Moroccan family segregating an apparently recessive phenotype of goiter, delayed psychomotor development, and stunted growth, which first came to medical attention in 1967. The 5-year-old female proband showed excretion of 50 to 70% of an administered dose of radiolabeled DIT, compared to controls who only secreted 15 to 20%, consistent with a diagnosis of deiodinase deficiency. The proband went on to have 5 children, 1 of whom was born with goiter and diagnosed with hypothyroidism due to dyshormonogenesis.
In 4 patients from 3 unrelated consanguineous families with hypothyroidism and biochemical features or a clinical history suggestive of an iodotyrosine deiodinase defect, Moreno et al. (2008) identified homozygosity for 3 different mutations in the iodotyrosine deiodinase (IYD) ... In 4 patients from 3 unrelated consanguineous families with hypothyroidism and biochemical features or a clinical history suggestive of an iodotyrosine deiodinase defect, Moreno et al. (2008) identified homozygosity for 3 different mutations in the iodotyrosine deiodinase (IYD) gene (612025.0001-612025.0003, respectively). Two of the patients were sisters whose consanguineous parents were members of the group of Scottish traveling families previously described by Hutchison and McGirr (1954, 1956). Afink et al. (2008) analyzed the IYD gene in a consanguineous Belgian Moroccan family segregating apparently recessive hypothyroidism and goiter consistent with deiodinase deficiency, and identified homozygosity for a missense mutation (612025.0003) in the proband and her affected daughter; 4 clinically unaffected offspring were heterozygous for the mutation. Six years after DNA testing, a heterozygous 14-year-old son developed nonautoimmune goiter and hypothyroidism, indicating dominant inheritance with incomplete penetrance, which Afink et al. (2008) noted had been previously suggested in some families (Codaccioni et al., 1970). The mutation was also found in 1 of 100 control alleles, suggesting that it might represent a functional SNP.