Poster Presentation ESA-SRB-APEG-NZSE 2022

Characteristics at presentation of neonates with Congenital Adrenal Hyperplasia secondary to 21-hydroxylase deficiency identified on a second-tier steroid profile newborn screening programme (#451)

Madeleine Hall 1 , Elmee Huda 2 , Mark Harris 1 3 , Ricky Price 4 , Brett McWhinney 5 , Jacobus Ungerer 3 4 5 , Carel Pretorius 3 4 5 , Tony Huynh 1 3 6
  1. Department of Endocrinology and Diabetes, Queensland Children's Hospital , Brisbane, Queensland, Australia
  2. Department of Paediatrics, Queensland Children's Hospital , Brisbane, Queensland, Australia
  3. School of Clinical Medicine, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  4. Newborn Screening Unit, Pathology Queensland, Herston, Queensland, Australia
  5. Department of Chemical Pathology, Pathology Queensland, Herston, Queensland, Australia
  6. Department of Chemical Pathology, Mater Pathology, South Brisbane, Queensland, Australia

Aim

To describe the biochemical, genetic, and clinical characteristics of a cohort of patients with congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency identified on a second-tier steroid profile newborn screening (NBS) programme.

Methods

A retrospective medical record review of neonates identified by a state-wide NBS programme between August 2020 to April 2022 was undertaken. Data collected included sex, gestational age, birth weight, timing of notification, CYP21A2 gene analysis, and clinical assessment and biochemistry at initial presentation.

Results

There were 18 NBS notifications however 2 extreme premature neonates died before confirmatory testing. The mean age at notification of 2nd tier results was 11 days (range 3-16). Mean age of clinical investigation for CAH was 7 days (range 1-15) with 11 as a direct result of NBS notification (7 males, including 2 sets of twins), 2 due to known 21-hydroxylase deficiency in a sibling, and 3 due to clinical concerns regarding ambiguous genitalia.

Equal males and females were identified, with the majority of females having minimal virilisation (6/8 Prader score of 2, 2/8 Prader score ≥ 3). Most neonates (12/16) were asymptomatic at initial assessment, with 1 male presenting in adrenal crisis, and 3 being described as lethargic (2 males, 1 female). Six neonates (4 males) had evidence of salt-wasting on initial presentation. One premature female (28 weeks gestation) had evidence of salt-wasting as early as day 3.

Fourteen neonates had mutations in CYP21A2 consistent with classical CAH while one had a genotype consistent with non-classical CAH, and has not commenced treatment. The remaining baby has not had CYP21A2 gene analysis but has a salt-wasting phenotype. 

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Conclusion

Given that typical clinical features of CAH may not be evident in the first week of life, especially in premature infants, early notification of NBS results are essential to avoid presentation with adrenal crisis.

  1. Speiser PW, Azziz R, Baskin LS et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103 (11): 4043-4088.
  2. Heather NL, Nordenstrom A. Newborn Screening for CAH-Challenges and Opportunities. Int J Neonatal Screen. 2021; 7(1): 11
  3. New MI, Abraham M, Gonzalez B et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 2013; 110(7):2611-6.