Clinical insights of the TBX19 C.856 C>T variant: a case report and literature review on neonatal isolated ACTH deficiency.

Objectives: Congenital isolated adrenocorticotropic hormone deficiency (IAD) is a rare condition often caused by variants in the TBX19 gene, leading to significant adrenal insufficiency and metabolic disturbances in neonates. Early recognition and treatment are significant for improving outcomes. Although the c.856 C>T (p.Arg286Ter) variant in TBX19 has been identified as pathogenic, little is known about the genotype-phenotype correlation due to the limited number of cases.

Case description: We present a male infant diagnosed with neonatal IAD, presenting with hypoglycemic seizures, hypokalemia, and cholestasis within the first 10 h postnatally. There was notable facial dysmorphism, including long philtrum, depressed nasal root, epicanthus, prominent low ears, and mild hypertelorism. A homozygous c.856 C>T (p.Arg286Ter) variant in TBX19 was identified by genetic analysis. After receiving hydrocortisone treatment, the patient showed normal growth and neurodevelopment by the age of 3.2, free from hypoglycemia or recurrent seizures.

Conclusions: Variants in TBX19, especially the c.856 C>T mutation, are a predominant cause of neonatal-onset adrenal insufficiency disorder (IAD). Prompt assessment of adrenal function in neonates presenting with hypoglycemia and cholestasis is essential for accurate diagnosis and timely initiation of hydrocortisone replacement therapy. Genetic assessment is essential for improving patient outcomes and advancing our comprehension of the relationship between genotype and phenotype.