ESPE Abstracts

Introduction: Congenital adrenal hyperplasia (CAH) describes a rare group of inherited conditions caused by enzyme defects within the steroid biosynthesis pathway. 21-hydroxylase deficiency accounts for approximately 95% of cases. The prevalence of even rarer forms of CAH varies according to geographical location and ethnicity.

Aims: To report the clinical characteristics of rare forms of CAH under the care of a tertiary children’s hospital between 2000 – 2023.

Methods: Patients with the ICD-10-CM code E25.0 “congenital adrenogenital disorders associated with enzyme deficiency” were identified. Electronic records were reviewed and only patients with CAH under endocrine follow-up were included. The final cohort consisted of 426 patients. This study was registered with the hospital QI office (registration number 3630).

Results: 94.4% had 21-hydroxylase deficiency, with 11β-hydroxylase deficiency (2.3%), 3β-hydroxysteroid dehydrogenase deficiency (1.6%), 17α hydroxylase/ 17,20-lyase deficiency (0.7%), P450 side-chain cleavage deficiency (0.7%) and aldosterone synthase deficiency (0.2%) making up the other enzymatic diagnoses. 17 (70.8%) of the non-21-hydroxylase deficiency diagnoses were confirmed by genetic testing. Ten patients had 11β-hydroxylase (CYP11B1) deficiency, seven of whom had confirmatory genetic results. Six had consanguineous parents. Five patients presented with peripheral precocious puberty but only two required GnRH agonist treatment. Three patients required anti-hypertensives. Four patients are still growing - their median hydrocortisone dose is 11.7 mg/m²/day. Of the seven patients with 3β-hydroxysteroid dehydrogenase (HSD3B2) deficiency, five were of Asian background and one had a history of parental consanguinity. Three patients had a genetic diagnosis; all homozygous for pathogenic HSD3B2 gene deletions. Patients presented with either ambiguous genitalia or hyponatraemic dehydration in infancy. The median hydrocortisone dose is 12.9 mg/m²/day for the four patients still growing. Two required GnRH agonist treatment and one also received an aromatase inhibitor. Three patients had genetically confirmed 17α-hydroxylase (CYP17A1) deficiency, all from consanguineous pedigrees. All three had a 46,XY karyotype. The two phenotypic females were diagnosed following incidental findings on cardiology investigation and genetic panel testing.

Conclusion: This large demographically-diverse CAH patient population reflects previously reported frequencies of CAH sub-types. Very rare forms of CAH may present incidentally or in late childhood. Genetic testing is often required to confirm clinical and biochemical findings. Most patients with HSD3B2 deficiency were of Asian background. Parental consanguinity was particularly prevalent in those with CYP11B1 and CYP17A1 deficiencies. Although precocious puberty was common in CYP11B1 deficiency, less than half required GnRH agonist therapy. Anti-hypertensive treatment was also uncommon, highlighting that adequate glucocorticoid treatment can limit these sequelae.