Long-term Follow-up of a Case with TBX19 Mutation, a Rare Cause of Isolated ACTH Deficiency and Literature Review.

T-box pituitary restricted transcription factor is a transcription factor required for proopiomelanocortin (POMC) gene expression and pituitary corticotroph cell differentiation and is encoded by T-box factor 19 (TBX19). Variants in TBX19 cause early onset congenital isolated adrenocorticotrophic hormone (ACTH) insufficiency with a mortality rate of up to 25% in the neonatal period. Mild dysmorphic findings may accompany some cases. Here, we report a case of isolated ACTH deficiency due to a TBX19 variant diagnosed in the neonatal period, who was followed up until adulthood. The male patient had hypoglycemia and convulsions on the first day of life and was subsequently evaluated for hypocortisolemia and low ACTH. While neonatal cholestasis and hyperbilirubinemia were prominent, facial dysmorphism was unremarkable. He was diagnosed with isolated ACTH deficiency, and hydrocortisone replacement therapy was initiated. TBX19 analysis revealed NM 005149 c.512T>C (p.Ile171Thr). Epileptic seizures were observed and antiepileptic treatment was initiated. Cranial magnetic resonance imaging revealed an arachnoid cyst, cortical atrophy, and gliotic changes. The patient was 22 years old at the last follow-up, and his physical and mental development were normal. Neuromotor development and growth were also normal. TBX19 variants present with hypoglycemic convulsions in the early hours of the neonatal period and may lead to life-threatening neonatal death. Early hydrocortisone replacement therapy is significant for survival without sequelae. Continuing to monitor patients for long-term issues and additional discoveries could be beneficial for elucidating the genotype-phenotype correlation.