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

TPIT is a transcription factor required for POMC gene expression and pituitary corticotroph cell differentiation and is encoded by TBX19. Variants in TBX19 cause early onset congenital isolated 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, which was followed up until adulthood. The patient with hypoglycemia and convulsions on the first day of life were 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 MRI revealed an arachnoid cyst, cortical atrophy, and gliotic changes. The patient, which was also included in the first case report describing the gene encoding TPIT, reached the final height. He was 22 years old at the last follow-up, and his physical and mental development was normal. Neuromotor development and growth were 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.