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

Al A. D. K., Kardelen Al A. D., Poyrazoǧlu Ş., Poyrazoglu S., Aslanger A. D., Aslanger A., ...Daha Fazla

HORMONE RESEARCH IN PAEDIATRICS, sa.6, ss.395-403, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1159/000506740
  • Dergi Adı: HORMONE RESEARCH IN PAEDIATRICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, SportDiscus
  • Sayfa Sayıları: ss.395-403
  • Anahtar Kelimeler: Isolated adrenocorticotropic hormone (ACTH) deficiency, TBX19mutation, Adrenal insufficiency, ISOLATED ADRENOCORTICOTROPIN DEFICIENCY, HORMONE DEFICIENCY, GENE MUTATION, EARLY-ONSET, TPIT, GROWTH, HYPOGLYCEMIA
  • İstanbul Üniversitesi Adresli: Evet

Özet

Introduction:Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare cause of adrenal insufficiency and T-box pituitary restricted transcription factor (TBX19) mutations are responsible for two-thirds of the neonatal onset form of the disease. IAD presents with hypoglycemia and prolonged jaundice in the neonatal period.TBX19is important for both pro-opiomelanocortin (POMC) gene transcription and differentiation ofPOMC-expressing cells. We describe 2 patients, 1 with a reported and 1 with a novelTBX19mutation, and present information about the long-term follow-up of these patients.Case Presentation:Both patients had critical illnesses, recurrent hypoglycemia, convulsions, and neonatal hyperbilirubinemia. They also had low cortisol and ACTH levels, while other pituitary hormones were within the normal range. Pituitary imaging was normal. After hydrocortisone treatment, there was resolution of the hypoglycemia and the convulsions were controlled. Genetic studies of the patients revealed both had inherited a homozygous mutation of theTBX19gene. The first patient had an alteration of NM_005149.3:c.856C>T (p.R286*) and the second patient had a novel NM_005149.3:c.584C>T (p.T195I) mutation, analyzed by next-generation sequencing. The noteworthy findings of the patients at follow-up were: short stature, microcephaly, and decreased pubic hair in the first, and dysmorphic features, Chiari type 1 malformation, tall stature, and low bone mineral density (BMD) in the second.Conclusion:Congenital IAD can be life-threatening if it is not recognized and treated early.TBX19mutations should be considered in the differential diagnosis of IAD. Further cases or functional analyses are needed for genotype-phenotype correlations. Low BMD, dysmorphic features, Chiari type 1 malformation, and sparse pubic hair are some of the important features in these patients.