Study of the associations between polymorphisms in genes related to the Thyroid hormone metabolic pathways and clinical outcome in hypothyroid children.

Αποτελέσματα της εργασίας παρουσιάστηκαν στο 4th ISNS Middle East-North Africa Regional Meeting, Limassol, Cyprus, March 8-11, 2020, “Introducing and expanding Newborn Screening in the MENA region”.

Gkika Anna1, Papathanasiou Mando1, Platis Dimitrios1, Voutetakis Antonis2, Mastorakos George3, Kanaka-Gantenbein Christina2, Girginoudis Panagiotis1, Joanne Traeger-Synodinos4 and Iliadi Alexandra1

1Institute of Child Health, Hellenic Newborn Screening Laboratory, Athens, Greece
3Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital
3Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION Hospital, Faculty of Medicine, National and Kapodistrian University of Athens
4Laboratory of Medical Genetics, National and Kapodistrian University of Athens

Introduction: Congenital hypothyroidism (CH) is the most frequently encountered Congenital Endocrinopathy, with a prevalence of 1:1500-3000 births, and may lead to mental subnormality if not diagnosed and treated promptly. Implementation of Neonatal Screening Programs for Congenital Hypothyroidism (CH) have reduced related nosologies and eradicated CH-associated mental impairment. The Hellenic Newborn Screening Program is carried out by the Institute of Child Health (ICH) which is also responsible for final diagnosis, treatment initiation and clinical and hormonal follow-up of CH patients. 

Objectives: The identification of biomarker-polymorphisms (SNPs) in genes associated with Thyroid hormones metabolic pathways that can be correlated with clinical features of CH, such as L-T4 replacement therapy response, would be an extremely valuable tool for the prognosis of the disease at a very early stage. Genetic analysis was focused on the detection of 6 single nucleotide polymorphisms (SNPs), rs1991517, rs225014, rs939348, rs4704397, rs12095080, rs11206244 in TSHR, DIO1, DIO2, THRa, PDE8B genes. The present study is the first attempt to correlate specific polymorphisms with clinical features in CH children with a known pathoetiology of the disease.

Methods: Laboratory, clinical and ultrasonographic data were recorded from the medical records of children diagnosed with CH by the Hellenic Neonatal CH Screening Program. Patients with specific inclusion criteria (n= 400): CH dyshormonogenesis/transient CH, age >3 years old, natural conception, monocytic pregnancy, non- syndromic, non- low birth-weight were selected.  DNA was isolated and genotyped with RE-PCR. Statistical analysis was performed to compare clinical features such as birth weight, gestational age, TSH and FT4 before LT-4 substitution, Guthrie TSH level, dose at 1 and 3 years and BMI at 3 and 5 years with different genotypes.

Results/Discussion: CH is a multifactorial and polygenetic disease with a variety of features and phenotypes. Identifying genetic biomarkers that might help us predict LT-4 substitution dose, clinical outcome/severity of disease is of paramount importance.