ESPEYB17 3. Thyroid Congenital hypothyroidism (3 abstracts)
3.7. DUOX2/DUOXA2 mutations frequently cause congenital hypothyroidism that evades detection on newborn screening in the UK
Peters C , Nicholas AK , Schoenmakers E , Lyons G , Langham S , Serra EG , Sebire NJ , Muzza M , Fugazzola L & Schoenmakers N
To read the full abstract: Thyroid. 2019;29:790–801.
Patients with mutations in the dual oxidase 2 (DUOX2 ) gene – encoding a NADPH oxidase that generates hydrogen peroxidase for iodide organification – have been repeatedly reported as not being detected by neonatal screening because it causes only mild hyperthyrotropinemia at birth. Here, Peters et al. determined the incidence of DUOX2 and dual oxidase 2 maturation factor (DUOXA2 ) mutations in patients with borderline blood spot TSH values. In a retrospective genetic study in 52 patients with thyroid gland in situ and borderline TSH, they detected a surprisingly high incidence (50%) of DUOX2 or DUOXA2 mutations. The key characteristic of mutation positive vs. mutation negative patients during the neonatal period was a significantly higher TSH on venous confirmatory testing or on second blood spot screening than on initial screening and lower mean FT4 values despite mild hyperthyrotropinemia.
These data provide clinically important answers: by current TSH cutoffs, we need to be aware that we will miss genetic forms of CH. Thus, clinical suspicion of this entity in the context of mild signs of hypothyroidism in neonates or infants should prompt retesting. However, the data also raise new questions: should TSH cutoffs be further lowered to better detect this mild dyshormonogenetic form of CH? Or should we perform targeted sequencing for DUOX2 and DUOXA2 in these patients? Biochemical diagnosis and genetic confirmation of mild dyshormonogenetic CH would argue for levothyroxine treatment at least during the sensitive early life neurodevelopmental time window. But is there enough evidence that these patients will benefit from early diagnosis and treatment? This chapter is not closed.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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