A Rare Presentation of Homozygous Pathogenic Variant in MC2R Gene with Salt-Wasting Crisis in a Neonate

Kardas Yildiz A., Bulbul A., Ozer Bekmez B., TÜRKYILMAZ A., Terali K., Dagdeviren Cakir A., ...More

Molecular Syndromology, vol.15, no.1, pp.77-82, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 1
  • Publication Date: 2024
  • Doi Number: 10.1159/000533986
  • Journal Name: Molecular Syndromology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.77-82
  • Keywords: Autosomal recessive, Familial glucocorticoid deficiency, Hyponatremia, MC2R gene, Newborn
  • Karadeniz Technical University Affiliated: Yes


Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare. Case Presentation: A term female neonate was admitted to the neonatal intensive care unit due to respiratory distress. On physical examination, she had generalized hyperpigmentation. Initial laboratory work-up yielded normal serum electrolytes and glucose. Hyponatremia and hyperkalemia emerged on follow-up. The patient was diagnosed as having primary adrenal insufficiency (PAI) with elevated plasma adrenocorticotropin hormone and reduced cortisol levels and hydrocortisone. We started on oral sodium (5 mEq/kg/day) and fludrocortisone (FC) (0.2 mg/day) treatment to the patient. Ultrasonography revealed hypoplastic adrenal glands. Molecular genetic analysis revealed a previously reported homozygous pathogenic variant NM_000529.2: c.560delT (p.V187fs∗29) in the MC2R gene. FC dose was tapered to 0.05 mg/day on the third month of life and was stopped at tenth months of age with maintenance of normal serum electrolytes and clinical findings. Conclusion: FGD due to MC2R gene mutation may rarely present with a salt-wasting crisis in the neonatal period. Identifying the causative gene with the pathogenic variant in PAI may serve to individualize a treatment plan.