Background: Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterized by low or absent cortisol production secondary to low plasma ACTH despite normal secretion of other pituitary hormones and the absence of structural pituitary defects. Mutations in the TBX19 gene, a T-box factor selectively expressed in developing corticotroph cells, have been identified so far only in cases of neonatal-onset complete IAD.
Objective and Hypotheses: Identify the IAD etiology.
Method: We present the case of a 23-month-old boy with a severe hypoglycemia and a generalized seizure during a viral episode with fever and vomiting. His cortisol and ACTH were undetectable. Other pituitary hormones were in the normal range and the brain MRI showed no pituitary defect. He was born full term to related Tunisian parents. The mother had gestational diabetes. He had a hypoglycemia few hours after the delivery thought to be secondary to the gestational diabetes with no detected recurrence in the first months of his life. He had a medical history of asthma with multiple hospitalizations, included one at 15 months with a long-fasting hypoglycemia noted. He has a regular growth. His older brother diagnosed with a combined pituitary hormone deficiency at 2 months, deceased at 24 months in a probable context of hypoglycemia.
Results: The TBX19 gene direct sequencing showed a homozygous recessive splicing site mutation previously described: IVS5+1G>A, leading to mRNA targeted for nonsense mediated decay and absence of protein expression.
Conclusion: This is a rare case with a late IAD diagnosis secondary to a TBX19 mutation. A TBX19 anomaly should not be rule out in patients without a neonatal diagnosis of IAD but still life threatening given its severity.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology