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Two rare forms of congenital adrenal hyperplasia, 11β hydroxylase deficiency and 17-hydroxylase/17,20-lyase deficiency, presenting with novel mutations

  • Krupali Bulsari
  • Louise Maple-Brown
  • Henrik Falhammar
Case Report



Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by deficiency of various enzymes responsible for adrenal steroidogenesis. 11-Beta-hydroxylase deficiency (11βOHD) and 17-hydroxylase/17,20-lyase deficiency (17OHD) are rare causes of CAH.


We hereby present a 65-year-old man with 11βOHD and a 33-year-old woman with 17OHD. The man with 11βOHD presented with peripheral precocious puberty and hypertension at age 15 years, fathered two children but developed complications of chronic glucocorticoid therapy on long-term follow-up. Interestingly, his younger sister had been diagnosed with the same condition at age 19 and had later given birth to four children while on glucocorticoids. Exome sequencing of the CYP11B1 gene detected the previously reported pathogenic mutation T318T (c.954G > A [p.Thr318Thr]) on one of the alleles and a novel mutation, R123G (c.367C > G [p.Arg123Gly]), on the other in a highly conserved region of the CYP11B1 gene. The woman with 17OHD presented with severe hypokalemia at age 22 years against a background of primary amenorrhea and lack of development of secondary sexual characteristics. She was heterozygous for a previously recognized mutation, R125Q (c.374G > A [p.Arg125Gln]), and a novel single base-pair deletion, G337fs (c.1010delG [p.Gly337Valfs*82]), which creates a frameshift with a new stop codon in the last exon of the gene, making it a likely pathogenic variant.


Recognition of novel mutations is clinically significant and will contribute to the understanding of the phenotype-genotype relationship of these rare disorders in the future. It also highlights successful fertility outcomes in 11βOHD which have not been well documented in the literature so far.


11 Beta-hydroxylase deficiency 17-Hydroxylase/17,20-lyase deficiency Congenital adrenal hyperplasia Fertility Long-term outcome 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Krupali Bulsari
    • 1
    • 2
  • Louise Maple-Brown
    • 1
    • 3
  • Henrik Falhammar
    • 1
    • 3
    • 4
    • 5
  1. 1.Department of EndocrinologyRoyal Darwin HospitalDarwinAustralia
  2. 2.Department of EndocrinologyPrincess Alexandra HospitalBrisbaneAustralia
  3. 3.Menzies School of Health ResearchDarwinAustralia
  4. 4.Department of Endocrinology, Metabolism and DiabetesKarolinska University HospitalStockholmSweden
  5. 5.Department of Molecular Medicine and SurgeryKarolinska InstitutetStockholmSweden

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