Two novel mutations of the thyroid peroxidase gene in two Japanese patients with congenital hypothyroidism (CH) detected by neonatal screening

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 596-623-Case Reports: Pediatric Endocrinology & Metabolism
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-619
Katsura Ishizu*1, Akie Nakamura1, Satoshi Narumi2, Tomonobu Hasegawa2 and Toshihiro Tajima1
1Hokkaido University School of Medicine, Sapporo, Japan, 2Keio University School of Medicine, Tokyo, Japan
Background: Thyroid peroxidase (TPO) is a key enzyme in the biosynthesis of thyroid hormone. The genetic impairment of the TPO gene is the cause of thyroid dyshormonogenesis among congenital hypothyroidism (CH), characterized by iodide organification defects. We identified two novel mutations of the TPO gene in two Japanese patients with congenital goitrous hypothyroidism detected by neonatal screening.

Case 1: The boy was born after 40 weeks of gestation by normal vaginal delivery from nonconsanguineous parents. There were no abnormal physical findings including goiter. Neonatal mass screening at 5 days of age showed elevated TSH (120 μU/ml). Further investigation showed that his serum TSH was 256.8 μU/ml and T4 was 4.3 μg/dl. L-T4 replacement therapy was initiated immediately. During follow up, a small goiter was noticed at 2 years of age.

Case 2: The boy was born after 38 weeks of gestation by normal vaginal delivery from nonconsanguineous parents. Neonatal mass screening at 5 days of age demonstrated elevated TSH (above 72.1 μU/ml) level and low freeT4 (0.35 ng/dl). Further evaluation showed that he had diffuse goiter and his serum TSH was 854.83 μU/ml and free T4 was 0.37 ng/dl, L-T4 replacement therapy was initiated immediately.

Results: Sequence analysis of the TPO gene demonstrated two novel mutations. Two compound heterozygous mutations were found in case 1: a missense mutation at c.1132G>A (p.E378K) and a 10 base deletion of intron 15- exon 16 boundary. In case 2, a homozygous missense mutation of p.E378K was identified.

Conclusions: We identified two novel mutations of the TPO gene in two Japanese patients with CH.

Nothing to Disclose: KI, AN, SN, TH, TT

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