Background: A 6-week-old male was admitted for investigation of prolonged jaundice. The pregnancy was unremarkable with a normal at term delivery. The neonatal screening was unremarkable. The boy was born to consanguineous parents of Turkish descent.
Objective and hypotheses: At presentation serum levels of thyrotropin, T4 and T3 were low and prolactin slightly elevated. Venous TSH was undetectable low. Central hypothyroidism was diagnosed and a TSH beta gene mutation was hypothesized.
Method: Using different PCR protocols, we were unable to amplify both coding exons of the boys TSHbeta gene, which suggested a deletion of the coding sequence. An array comparative genomic hybridization (aCGH) was performed using specific probes around the TSHbeta gene locus on chromosome 1.
Results: The propositus was homozygous for a 6 kb deletion spanning all exons, as well as parts of the 5 UTR of the TSHbeta gene. Both parents were heterozygous for this deletion.
Conclusion: This is the first report of a large deletion in the TSH beta gene. Isolated congenital secondary hypothyroidism (ICSH) is rare but important, since most patients with ICSH are diagnosed later in life, which results in severe growth failure and intellectual disability. Our study shows again that neonatal screening for both, fT4 and TSH is desirable. It would help to prevent symptoms of hypothyroidism in affected individuals.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology