Navoda Wickramasinghe¹, Jagath Ranasinghe¹, Kayalvily Perinpanayagam², Jananie Suntharesan³
1- District General Hospital, Nawalapitiya, Sri Lanka
2- Apeksha Hospital, Sri Lanka
3- Sirimavo Bandaranayake Specialized Children’s Hospital, Sri Lanka
Abstract Body
Introduction: Congenital Adrenal Hyperplasia (CAH) is a rare form of primary adrenal insufficiency caused by autosomal recessive inheritance primarily of 21 hydroxylase deficiency . Severity depends on the degree of residual enzyme activity . Patients present with classical form during early neonatal period with salt loosing/virilization. Non-classical form presents later with virilization. We present a rare case of CAH without virilization.
Case presentation: 4- Years-old girl presented with fever, cough, difficulty in breathing for oneday with Addisonian crisis. She was pigmented without virilization. Parents were consanguineous and three of her elder siblings had died during the infancy or early childhood. Cause of death was presumed sepsis. She had failure to thrive with marginal developmental delay . Investigations revealed high ACTH, low cortisol and high renin level. Karyotype 46,XX. Pretreatment and post treatment testosterone and 17-hydroxyprogesterone was low . Allele specific PCR followed by next generation sequencing revealed heterozygous positive for P30L, I2G, 8 Bp deletion, I172N, E6 cluster, V281L, Q318X and R365W hotspot mutations in the CYP21A2. Parental blood was not available to confirm compound heterozygosity .
Conclusion: Despite the presence of pathogenic CYP21A2 variants consistent with severe 21- hydroxylase deficiency , the patient demonstrated persistently low 17-hydroxyprogesterone and testosterone in the setting of markedly elevated ACTH. This biochemical profile suggestsnear-complete adrenal steroidogenic failure rather than a classical precursor accumulation pattern. Similar presentations have been described in rare cases of severe CYP21A2 disruption, where extensive gene deletions or complex pseudogene conversions result in functional adrenal insufficiency with overlapping features of congenital adrenal hyperplasia and primary adrenal failure.