A Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Caused by Two Novel Mutations in the TBX19 Gene

Abstract

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (CIAD) is a rare disorder which can result in 20% mortality in the neonatal period if misdiagnosed. A 2 years and 7 months old boy was hospitalized many times because of recurrent hypoglycemia. On initial physical examination, the patient showed special appearance and indications of fast growth (≥P97). Laboratory investigations revealed low levels of ACTH and cortisol in his plasma. Except thyroid-stimulating hormone, the anterior pituitary hormone concentrations were normal. Molecular data showed compound heterozygosity for two novel mutations in the TBX19 gene (encoding the transcription factor T-Box 19). Mutation c.205C>T was inherited from mother and the fragment deletion (from g.168,247,374 to g.168,278,264) was from father. Hydrocortisone replacement therapy was effective. We reported two novel TBX19 mutations, expanding the mutation spectrum of this disorder, in a CIAD patient who presented with special appearance, signs of fast growth, and thyroid-stimulating hormone derangement. In addition, for avoiding misdiagnosis, criterion for ACTH and cortisol detection of CIAD should be established.

A Rare Cause of Adrenal Insufficiency – Isolated ACTH Deficiency Due to TBX19 Mutation: Long-Term Follow-Up of Two Cases and Review of the Literature

“…Alsaleem et al [20] Akcan et al [21] Unal et al [22] Abalı et al [12] Weijing et al [15] Our study had tall stature even though she had a low IGF1 level. They suggested that glucocorticoids inhibit IGFBP5.…”

“…A lack of inhibition of IGFBP5 due to cortisol deficiency in IAD patients may have an underlying mechanism that promotes tall stature. Weijing et al [15] reported a similar growth pattern, but their patient had a normal IGF1 level; the tall stature was normalized after starting hydrocortisone. Similarly, our second patient was of tall stature with a normal IGF1 level; at follow-up once on treatment, her growth was within the normal range.…”

“…Previously, some dysmorphic features of patients were reported, but these are not common in TBX19 mutations [3, 15]. Arnold-Chiari type 1 malformation was found in 2 patients [6].…”

A serious and unusual presentation of congenital isolated ACTH deficiency due to TBX19 mutation, beyond the neonatal period

“…Heredity is autosomal recessive, with homozygous or compound heterozygous individuals expressing the disease. In a series of 91 patients with IAD, Couture et al described 21 different TBX19 mutations (4); however, new mutations have been identified since (7,8).…”

Congenital Isolated ACTH Deficiency Caused by TBX19 Gene Mutation: A Family Report

“…This disease is documented mostly in case reports or series. If pediatricians fail to recognize this disease in the neonatal period, it can result in 20-25% mortality (4,5).…”