A novel mutation in thyroglobuline gene identified in a boy with giant goiter

RIVOLTA CARINA M; SANTUCCI ZULMA C; BALBI VIVIANAA; ADROVER, EZEQUIELA; TOURNIER ANDREA L; GONZALES VERÓNICA G; TARGOVNIK , HÉCTOR M; SIFFO, SOFÍA; MORIN ANALÍA

Washington D.C.

Congreso; 10th International Meeting of Pediatric Endocrinology; 2017

PES-APEG-APPES-ASPAE-CSPEM-ESPE-JSPE-SLEP

Objectives: Patients with thyroglobuline (Tg) synthesis defects show goiter. Several mutations have been identified in them. The aim was to present a patient with giant goiter and a mutation of Tg gene. Methods: Case report. A 12-yr-old boy presented with progressive goiter. Four months before, he noted an augmented and sudden swelling without dysphagia. He had been treated with levothyroxine (LT), but he had stopped it. Familial antecedents. Father was born in Salta, Argentina. Mother was born in Bolivia. No familial thyroid diseases. Physical exam. Puffy facies, coarse voice, yellowish earthy pallor and dry skin. Giant goiter with firm consistence. Results: Laboratory data. TSH 76.7 μUI/ml (NR: 0.5-5); T4 3.7 μg/dl (6.09-12.23); T4l 0.17 ng/dl (0.58-1.24); TPO and Tg Ab negative. Cardiovascular control: minimal pericardial effusion. Thyroid ultrasound. Gland size augmented with multiple rounded echogenic images in both lobes, adenomatous hyperplasia. Right lobe: 114 x 51 x 52.4 mm. Left lobe: 109 x 48.3 x 49.6 mm.Treatment. LT 100 μg/d. Fine needle biopsy. Hyperplasia in follicular-epitelial cell flaps, with minimal focal anisocariosis. Surgery was indicated. He persisted with big goiter, with irregular surface. Laboratory. TSH 4.47 uUI/ml; T4 1.8 ug/dl; T4l 0.22 ng/dl; T3 284 ng/dl receiving LT at an adequate dose. Tg 0.2 ng/ml. Molecular biology sample was taken to study Tg gene. Surgery was performed one year later because of presence of multinodular goiter. Anatomopathology. Total thyrodectomy. Piece weight 229 grs. Irregular surface, predominantly solid light brown colour, with little cavities. Microscopic exam samples revealed folicles with epitelial hyperplasia, others with very much dilated lights of varied sizes between folicles septum of connective tissue that clutter as nodules. Molecular biology analysis. DNA sequencing identified the presence of a novel c.7093T>C [p.W2346R] homozygous mutation in the Tg gene. Diagnosis. Nodular hyperplasia. Multinodular goiter. Follow up. Although repeated titrations of LT dose, TSH persisted elevated and T4 low, with frequent missed doses. Conclusions: A new mutation in the region of homology to the acetylcholinesterase, (ACHE-like) p.W2346R in homocigozity that affect intracelular Tg transport has been found.