Familial glucocorticoid deficiency due to a novel TXNRD2 variant: expanding the spectrum of a rare genetic cause
By
Ibrahim Al Alwan
Kheloud M. Alhamoudi
Abdullah Ibrahim Alzaben
Beshaier Almulhem
Nawal Qawasmi
Meshael Alswailem
Sara Alotaibi
Burair Alsaihati
Amjad Jabaan
Moeber Mahzari
Christa E. Flück
Ali S. Alzahrani
May 28, 2026
Clinical Scorecard: A Novel TXNRD2 Variant Linked to Familial Glucocorticoid Deficiency: Broadening the Understanding of This Rare Genetic Condition
At a Glance
Category Detail
Condition Familial Glucocorticoid Deficiency (FGD) Key Mechanisms Impairment of mitochondrial redox balance due to TXNRD2 variant Target Population Individuals with autosomal recessive inheritance of FGD Care Setting Clinical genetics and endocrinology
Key Highlights
FGD is characterized by isolated cortisol deficiency and elevated ACTH levels. A novel homozygous TXNRD2 variant (c.575C>T) was identified in a Saudi family. The variant affects a highly conserved residue and is predicted to be deleterious. Only four biallelic TXNRD2 variants have been reported in FGD patients. TXNRD2 plays a critical role in maintaining mitochondrial redox balance. Guideline-Based Recommendations
Diagnosis
Confirm diagnosis with low cortisol levels and elevated ACTH levels. Management
Treatment with hydrocortisone to manage adrenal insufficiency. Monitoring & Follow-up
Regular monitoring of cortisol and ACTH levels. Risks
Potential for severe dehydration and electrolyte imbalances. Patient & Prescribing Data
Patients with familial glucocorticoid deficiency due to TXNRD2 variants.
Hydrocortisone dosage should be adjusted based on body surface area.
Clinical Best Practices
Consider genetic testing for TXNRD2 in patients with unexplained adrenal insufficiency. Monitor for neurological complications in patients with FGD. Related Resources & Content
