title: Delayed onset congenital hypothyroidism in a patient with DUOX2 mutations and maternal iodine excess.
abstract: Congenital hypothyroidism (CH), one of the most common congenital endocrine disorders, causes irreversible intellectual disability in untreated patients. Today, the vast majority of patients receive early diagnosis and treatment in the context of newborn screening for CH, and achieve satisfactory cognitive development. However, a subset of patients with delayed onset are undetectable by newborn screening, and miss benefit from early intervention. Here, we report on a delayed-onset CH patient that had two contributing factors in the pathogenesis of CH simultaneously, i.e., a genetic defect and iodine excess. The patient was exposed to excessive iodine in utero because her mother consumed massive amounts of seaweed during pregnancy. Surprisingly, the patient had a negative result in newborn screening, but developed overt CH at age 3 months. She received thyroxine supplementation until when normalization of the thyroid function was confirmed at age 3 years (i.e., transient CH). Mutation screening for DUOX2, a causative gene for transient CH, showed biallelic mutations (p.[E327X] + [H678R]). This report provides a new example of environmental modification of phenotypes of CH due to a genetic defect, which can potentially distort screening results.
authors.affiliation: Department of Pediatrics, Higashitoyonaka Watanabe Hospital, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kasahara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Narumi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okasora
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Takaya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000483:Alleles; D002648:Child; D003409:Congenital Hypothyroidism / Q000188:drug therapy / Q000235:genetics*; D019587:Dietary Supplements / Q000009:adverse effects*; D000074623:Dual Oxidases; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007455:Iodine / Q000009:adverse effects* / Q000097:blood; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D015997:Neonatal Screening; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy / Q000235:genetics*; D012624:Seaweed; D013974:Thyroxine / Q000008:administration & dosage
chemical_list: D007455:Iodine; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; D013974:Thyroxine