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Licensed Unlicensed Requires Authentication Published by De Gruyter February 28, 2019

Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature

Thomas Breil, Vira Yakovenko, Ioana Inta, Daniela Choukair, Daniela Klose, Janna Mittnacht, Egbert Schulze, Abdul Alrajab, Jürgen Grulich-Henn and Markus Bettendorf

Abstract

Background

11β-hydroxylase deficiency (11βOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5–8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11βOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11βOHD.

Methods

Clinical, biochemical and radiological data of patients with 11βOHD were analysed in this retrospective single-centre analysis.

Results

Six male patients of four unrelated families with 11βOHD were identified (0.1–13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA–CA: 5.5 years, range 1.5–9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11βOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years.

Conclusion

The diagnosis of CAH due to 11βOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11βOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.


Corresponding author: Thomas Breil, MD, Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany
aThomas Breil and Vira Yakovenko contributed equally to this work.

Acknowledgements

We are grateful to Nils Janzen for the retrospective analysis of 11-deoxycortisol in the blood spots of the newborn screening card of patient 2B.

  1. Compliance with ethical standards

  2. Conflict of interest: The authors declare that they have no conflict of interest.

  3. Informed consent: Informed written consent was obtained from all individual participants included in the study.

  4. Ethical approval: All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Article note

This work was presented in part at the 53rd annual meeting of the European Society of Paediatric Endocrinology (ESPE) 2014 in Dublin, the Republic of Ireland.


Received: 2018-07-09
Accepted: 2018-12-30
Published Online: 2019-02-28
Published in Print: 2019-03-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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