Transient Congenital Hypothyroidism Due to Biallelic Defects in DUOX2 Gene

ENACAN, R; MASNATA, M; PAPENDIECK, PATRICIA; BELFORTE, FIORELA S.; TARGOVNIK , HECTOR M.; GRUNEIRO-PAPENDIECK, LAURA; RIVOLTA, CARINA M.; CHIESA, ANA

Puerto Varas

Congreso; XXV Annual Meeting, SLEP; 2015

Sociedad Latinoamericana de Endocrinologia Pediatrica

Introduction: Dual oxidases (DUOX1 and 2) are components of the thyroid hidrogen peroxide (H2O2) generating system needed for the thyroid hormone organification. Mutations in the DUOX2 gen (DUOX2) have been described in transient and permanent congenital hypothyroidism (CH) presenting with goiter and positive perchlorate discharge test. Subjects and Methods: We report two siblings born from unrelated healthy parents. The eldest was detected through neonatal screening with slightly elevated TSH. At 1 month she was treated with LT4 with TSH: 32 mU/l, T4 13 ug/dl, FT4: 1.46 ng/dl and TG: 266 ng/dl (Normal reference (NR): 30?100) and goiter in the Tc99 scan. Treatment was withdrawn at 2.9 years of age when she showed normal TSH, T4 and FT4 levels and TG: 41.7 ng/dl (NR 6-30). Perchlorate discharge was 17% (normal <15%). Treatment was restarted and stopped again at 7 years. A month later thyroid profile was normal, perchlorate test negative and TG: 51.2 ng/dl. She is now 12 years old, grows normally, undergoes normal puberty and keeps euthyroid. Her brother, also positive for CH screening, started treatment at age 15 days (TSH: 33 mU/l, T4: 7.9 ug/dl, FT4: 0.9 ng/dl and TG: 666 ng/dl). Reevaluation at 3.3 years showed normal thyroid profile and negative perchlorate test. With 7 years of age he is euthyroid and grows normally. With suspicion of organification disorder, all 17 exons of the TPO gene (TPO) and the 33 exons of the DUOX2 were studied by SSCP. Afterwards DNA sequence analysis was performed with Sanger technic in all fragments with abnormal migration.Results: SSCP revealed no abnormalities in the TPO. Regarding DUOX 2, in both patients, a novel deletion in exon 9 (c.1057_1058delTT, p.F353 fsX388) of the paternal allele and an already described mutation in exon 11 (c.1271t>g, p.Y425X) in the maternal allele were found. Their healthy brother harbored only the exon 11 mutation.Conclusion: Molecular TPO and DUOX evaluation should be carried out when permanent o transient organification disorders are suspected. As our findings confirm, the magnitude of the defect is not related to the number of inactivated alleles. Biallelic defects of DUOX2 in transient CH infers compensatory mechanisms in the peroxide supply.