Endocrine Abstracts

Introduction: MIRAGE syndrome is a rare disorder characterized by Myelodysplasia, Infections, Restriction of growth, Adrenal hypoplasia, Genital phenotypes and Enteropathy, caused by a mutation in the SAMD9 gene. The genital phenotypes are variable, ranging from hypospadias to complete female phenotype in 46,XY patients, while 46, XX patients may have dysgenetic ovaries. Mortality is high, with a median survival of 3 years; death is typically due to recurrent infections.

Case presentation: We report the case of a 1-month-old female preterm infant (born at 27 weeks’ gestation; birth weight 640 g; -1.77 SDS) who presented critically unwell with hypotension resistant to inotropic support but responsive to hydrocortisone, and recurrent episodes of hyponatremia. The clinical picture was also complicated by respiratory distress syndrome, sepsis, thrombocytopenia and conjugated hyperbilirubinemia. Initial blood tests revealed low cortisol (<0.3 nmol/l), TSH (1.4 mIU/l) and FT4 (7.2 pmol/l). Replacement therapy with hydrocortisone and levothyroxine was started. Further assessment of the pituitary function showed high ACTH (92 ng/l) while IGF1, LH and FSH were normal. The adrenal insufficiency work-up showed high renin (> 23.7 nmol/l/h) and low aldosterone (< 50 pmol/l), DHEAS (< 0.4 umol/l), 17-OHP (< 0.3 nmol/l) and androstenedione (< 0.7 nmol/l). Abdominal ultrasound documented absent adrenal tissue bilaterally, suggesting congenital adrenal hypoplasia. Fludrocortisone was also commenced. Further examination raised concerns of genital ambiguity (prominent clitoris and large labia majora). Investigations revealed a 46,XY karyotype, high inhibin B (346 pg/ml) and AMH (701.3 pmol/l), along with low testosterone (0.3 nmol/l) and 5DHT (< 0.25 nmol/l). Pelvic ultrasound showed absent uterine and ovarian tissue, with gonads located bilaterally in the groins. Genetic investigation identified a heterozygous pathogenic SAMD9 variant (c.2920G>A p.(Glu974Lys)), consistent with MIRAGE syndrome. Despite intensive care, the infant passed away at 2 months of age.

Conclusion: MIRAGE syndrome should be suspected in infants with adrenal insufficiency and multisystem involvement, particularly when the clinical course is different from that typically expected for a sick infant. Diagnosis may be challenging due to the overlapping features with complications of prematurity.