Evaluation of growth and puberty in a child with a novel TBX19 gene mutation and review of the literature
Biallelic mutations in the TBX19 gene cause severe early-onset adrenal failure due to isolated ACTH deficiency (IAD). This rare disease is characterized by low plasma ACTH and cortisol levels, with normal secretion of other pituitary hormones. Herein, we report a patient with IAD due to a novel TBX19 gene mutation, who is also of tall stature.
A 48/12-year-old girl was presented with loss of consciousness due to hypoglycemia. The patient was born at term with a birth weight of 3800 g. Her parents were first-degree cousins. She had a history of several hospitalizations for recurrent seizures, abdominal pain, and vomiting. At presentation, her weight and height were + 1.8 and + 2.2 SDS, respectively. Serum glucose was 25 mg/dl (1.4 mmol/L), with normal sodium, potassium, and insulin concentrations. The child was hypocortisolemic (0.1 μg/dl), and ACTH levels were extremely low (< 5.0 pg/ml). A diagnosis of IAD was made and hydrocortisone treatment was started. Hypoglycemic episodes, seizures, and recurrent gastrointestinal complaints disappeared after hydrocortisone replacement. Magnetic resonance imaging of the pituitary was normal. Whole exome sequencing revealed a novel homozygous c.302G > A (W101*) mutation in the TBX19 gene.
We report a new mutation in the TBX19 gene in a patient with isolated ACTH deficiency. While overgrowth is a known feature of some types of adrenal insufficiencies, including MC2R gene defects and POMC deficiency, it may be a novel feature for TPIT deficiency, as in our patient.
KeywordsTPIT TBX19 Isolated ACTH deficiency Growth Puberty Central adrenal insufficiency
The authors wish to express their gratitude to the parents and the patient who participated in this study.
Zehra Yavas Abali, Gozde Yesil, Tarik Kirkgoz, Sare Betul Kaygusuz, Mehmet Eltan, Serap Turan, Abdullah Bereket, and Tulay Guran conceptualized and designed the study. Zehra Yavas Abali and Tulay Guran drafted the initial manuscript. Serap Turan, Abdullah Bereket, and Tulay Guran critically reviewed the manuscript. Gozde Yesil and Tulay Guran performed the assays, analyzed data, and interpreted the results. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The patient’s parents provided informed consent for publication of the submitted article and the results of the accompanying genetic analyses.
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