Endocrine Abstracts

Objective: To describe the phenotypic and molecular characteristics of familial thyroid dyshormonogenesis (FTDH) in the Tunisian population.

Patients and Methods: A retrospective descriptive study including two related (R and K) with high consanguinity whose members are carriers of FTDH. Biological and genetic screening was proposed for all consenting members.

Results: FTDH was identified in 11 patients (8 girls, 3 boys) with a mean age of 4 years and 3 months (range: 1 month-17 years). The family screening revealed 10 other members with hypothyroidism not related to FTDH. At diagnosis, 63.6% of the patients were clinically hypothyroid vs 36.4% with apparent euthyroidism who were diagnosed through the family survey. Mental retardation was detectable in 4 children. Three patients also had sensorineural deafness. Three patients had a homogeneous goiter. Mean TSH and T4 were 24.19 mIU/l and 4.73 pmol/l, respectively. The antithyroid antibodies positivity rate was 18.2%. Substitution therapy (mean dose=125 mg/d) resulted in euthyroidism in all patients. After a mean follow-up of 11.88 years, three patients required thyroidectomy for compressive and/or nodular goiter. Molecular analysis revealed a single mutation (c.875 C> T) (p.S292F) in the TPO gene with recessive inheritance.

Discussion: FTDH is responsible for 15-20% of congenital hypothyroidism cases that can lead to severe neurosensory complications. In the Tunisian population, the TPO gene mutations are the most frequent and would be amplified by a founder effect in certain regions with high rates of consanguinity and endogamy.

References: 1. Kwak, Min Jung. "Clinical genetics of defects in thyroid hormone synthesis." Annals of Pediatric Endocrinology & Metabolism 23.4 (2018): 169.2. Cangul, Hakan, et al. "Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community." Clinical endocrinology 79.2 (2013): 275-281.