Molecular genetics of congenital adrenal hyperplasia (21-hydroxylase deficiency): implications for diagnosis, prognosis and treatment
Abstract
The molecular genetics of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency are reviewed. In Sweden, mutation detection based on allele‐specific PCR has been used for genetic diagnosis of this disease since 1993. Around 400 affected 21‐hydroxylase genes have been analysed so far. An update of the spectrum of mutations among the Swedish patients shows that nine common pseudogene‐derived mutations are responsible for the disease in around 95% of alleles. A total of 13 rare, mostly population‐specific mutations have been characterized among the remaining 5%. The mutations can be divided into different groups according to severity. This makes it possible to predict clinical outcome in affected subjects based on genotyping. The risk of salt‐wasting and prenatal virilization can be estimated, and over‐treatment can be avoided in mildly affected cases.
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In NC CAH, the estimated residual enzymatic activity of CYP21A2 is about 20-50% based on in vitro or in silico studies, resulting in a generally mild but highly variable phenotype.
“In NC CAH the estimated residual enzymatic activity of CYP21A2 is about 20 -50% based on in vitro or in silico studies, resulting in a generally mild but highly variable phenotype (212,217,416).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [217]
Some studies report normal resting and 24-hour blood pressure profiles whereas others report a slight increase of either diurnal or both diurnal and nocturnal systolic blood pressure, compared to matched controls even in childhood.
“Some studies report normal resting (217,626,675) and 24-hour blood pressure profiles (676) whereas others report a slight increase of either diurnal or both diurnal and nocturnal systolic blood pressure, compared to matched controls even in childhood (677,678).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [217]
Metabolic syndrome was observed in nearly 20% of adults in the NIH's cross-sectional study cohort, associated with older age but not with androgens, glucocorticoid type, or dose.
“Metabolic syndrome was observed in nearly 20% of adults in the NIH's cross-sectional study cohort (217), associated with older age but not with androgens, glucocorticoid type, or dose.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [217]
The prevalence of overweight and obesity are greater in adults with CAH in the UK and Sweden but similar to the general population in the US and France.
“The prevalence of overweight and obesity are greater in adults with CAH in the UK (360) and Sweden (671) but similar to the general population in the US (217) and France (626,672).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [217]
A few studies have reported normal or even high BMD, but most have shown low BMD at all or at least some sites in patients with CAH.
“A few studies have reported normal (704-709) or even high BMD (710), but most have shown low BMD at all or at least some sites (209,217,360,646,711-722).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [217]
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“Instead, a longer control fragment, representing CYP21P, is produced (19).”
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Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
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The Complexities in Genotyping of Congenital Adrenal Hyperplasia: 21-Hydroxylase Deficiency
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- Authors
- Wedell, A.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Wedell, A
- Venue
- Acta Paediatrica
- Publisher
- Wiley
- Published
- 1998-02
- Volume
- 87
- Issue
- 2
- Pages
- 159-164
- ISSN
- 0365-1436 (ISSN-L)
- 0803-5253
- 1651-2227
- OpenAlex
- W4233500203
- Cited by
- 73
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 6 · 2012: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Paediatrica (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital adrenal hyperplasia, 21-hydroxylase deficiency, CYP21 mutations, mutation spectrum, allele-specific PCR, genetic diagnosis, prognosis, salt wasting, overtreatment, Swedish patients
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