The homozygous deletion c.2422delT in the carboxyl-terminal coding region of the hTPO gene results in a frameshift mutation and leads to an early stop codon in exon 14 of the gene (p.Cys808AlafsX24). Combination with double heterozygous DUOX2 mutations was also reported. We present the data on the clinical course of CH in three patients with permanent congenital hypothyroidism (CH) harboring one and the same mutation. Pat1 was followed 29 yrs; after an uneventful pregnancy (no consanguinity) and vaginal delivery she was diagnosed at 38d by clinical signs (severe prolonged jaundice due to indirect hyperbilirubinemia, constipation, feeding difficulties, edema, delayed bone age, hoarse voice) before the screening introduction. She was started on L-thyroxin (25 mcg/d) on d36 (pretreatment TSH >43 mU/l, fT4 1.2 pmol/l), adjustments were performed, but TSH was often above 5 mU/l. The development milestones were normal, she had excellent marks during school attention, graduated and is working. Her younger brother was diagnosed at d10 (TSH 368 mU/l, fT4 0.7 pmol/l), L-T4 was given initially at a dosage of 25 mcg/d (10 days) and 50 mcg/d thereafter. Normal motoric and intellectual development were noticed, an eutopic thyroid as well. Pat3 was picked up by TSH screening (NTSH 238 mU/l d3), the high CH suspicion was confirmed on d22 (TSH>900 mU/l, T4 <20 nmol/l, Tg 490 ng/ml) and 50 mcg/d L-T4 were given. His thyroid volume increases with elevation of the TSH (several times) and multinodular goiter developed bilaterally, therefore the thyroid was extirpated at 19 yrs. After informed consent molecular analysis of the hTPO gene (Sanger sequencing) was performed in all three patients and the same homozygous previously described mutation c.2422delT could be detected. In conclusion: follow up data combined with molecular genetics could help in personalizing the treatment (no re evaluation needed) and facilitate the possibilities for genetic consultation. Thyroid US (at diagnosis and during follow up), in CH patients with eutopic glands combined with frequent hormonal controls are highly advisable.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology