Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene

Exp Clin Endocrinol Diabetes DOI: 10.1055/a-1108-1419Congenital Adrenal Hyperplasia is a group of genetic autosomal recessive disorders that affects adrenal steroidogenesis in the adrenal cortex. One of the most common defects associated with Congenital Adrenal Hyperplasia is the deficiency of 21-hydroxylase enzyme, responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. The impairment of cortisol and aldosterone production is directly related to the clinical form of the disease that ranges from classic or severe to non-classic or mild late onset. The deficiency of 21-hydroxylase enzyme results from pathogenic variants on CYP21A2 gene that, in the majority of the cases, compromise enzymatic activity and are strongly correlated with the clinical severity of the disease. Due to the exceptionally high homology and proximity between the gene and the pseudogene, more than 90% of pathogenic variants result from intergenic recombination. Around 75% are deleterious variants transferred from the pseudogene by gene conversion, during mitosis. About 20% are due to unequal crossing over during meiosis and lead to duplications or deletions on CYP21A2 gene. Molecular genetic analysis of CYP21A2 variants is of major importance for confirmation of clinical diagnosis, predicting prognosis and for an appropriate genetic counselling. In this review we will present an update on the genetic analysis of CYP21A2 gene variants in CAH pati...
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: Tags: Review Source Type: research

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Purpose of review Data on the long-term cardio-metabolic outcomes classical congenital adrenal hyperplasia (CAH) patients have been published with controversial results. Conventional treatment recommends hydrocortisone during childhood; and short and/or long-acting glucocorticoid during adulthood, associated or not with mineralocorticoid, in an attempt to simulate normal cortisol secretion and to normalize androgen excess. However, the balance between glucocorticoid over or undertreatment is very challenging, and patients frequently oscillate between hypercortisolism or hyperandrogenism. Considering these data, we review...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: ADRENAL CORTEX AND MEDULLA: Edited by Irina Bancos Source Type: research
In this report, we describe a pair of monozygotic twins with classic simple virilising form of CAH, who had a simultaneous onset and similar severity of clinical manifestations. Genetic analysis of the CYP21A2 gene in twin 1 showed the pres-ence of two heterozygous pathogenic sequence variants, c.518T>A and c.955C>T in the CYP21A2 gene, consistent with a diagnosis of CAH due to 21-hydroxylase deficiency. We also present a brief review of previous cases of twins with CAH. PMID: 32272826 [PubMed - as supplied by publisher]
Source: Pediatric Endocrinology, Diabetes, and Metabolism - Category: Endocrinology Authors: Tags: Pediatr Endocrinol Diabetes Metab Source Type: research
Publication date: October 2019Source: Canadian Journal of Diabetes, Volume 43, Issue 7, SupplementAuthor(s): Erin Miller, Janine Malcolm, Erin Keely
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
This study examined the potential impact of congenital adrenal hyperplasia on sexuality among male patients. What have we learned?Journal of the Endocrine Society
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Diabetes & Endocrinology Journal Article Source Type: news
Exp Clin Endocrinol Diabetes 2019; 127: 171-177 DOI: 10.1055/a-0820-2085The introduction of newborn screening programmes in most Western countries for classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) enables timely introduction of life-saving glucocorticoid replacement in affected babies. Early diagnosis and optimised pediatric care not only successfully led to survival but also allow that almost all patients reach adulthood. Cohort studies in adults, however, provided evidence for significant health problems and co-morbidities of adult patients such as life-threatening adrenal crises, cardiova...
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: Tags: Review Source Type: research
This article reviews these arguments using an ethical framework and discusses the application and challenges of recent disorders of sex development research. Recent findings Recent ethics literature and advocacy groups have argued for deferring genitoplasty until a child reaches decisional maturity. As a counterpoint, urological societies have published arguments supporting the practice of early genitoplasty. Data from DSD research lends some guidance but also has a wide range of outcomes, which makes generalizability difficult. A retrospective, multicenter study of 21 individuals with congenital adrenal hyperplasia who...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: GROWTH AND DEVELOPMENT: Edited by Lynne L. Levitsky Source Type: research
Discussion Potassium (K+) is an alkali metal (Group 1 of periodic table with Hydrogen, Lithium and Sodium) with an anatomic number of 19. Its chemical symbol K, comes from the medieval Latin, kalium which means potash (mainly potassium carbonate or potassium hydroxide), the substance it was first isolated from. Potassium is an important cation and it mainly resides in the intracellular fluid with only a small amount in the extracellular fluid. Potassium regulates cell volume, pH and enzyme functions. Hyperkalemia is defined as a potassium level> 5.5 mEq/L in children and> 6.0 mEq/L in newborns. Hyperkalemia incre...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder caused by mutations in the CYP21A2. Congenital nephrogenic diabetes insipidus (NDI) is a rare X-lin...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Case report Source Type: research
Purpose of review Monogenic disorders play significant roles in the pathogenesis of childhood-onset primary adrenal insufficiency (PAI). The most common form of PAI is congenital adrenal hyperplasia (CAH), which includes the enzymatic defects of the steroidogenic pathway. This review focuses on less common forms of monogenic PAI (i.e. non-CAH monogenic PAI) with particular attention on their cause, clinical phenotypes and genetic epidemiology. Recent findings Non-CAH monogenic PAI can be classified into three major categories: first, adrenocorticotropic hormone resistance, second, impaired adrenal redox homeostasis an...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya Source Type: research
Purpose of review Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a relatively common inherited disorder of cortisol biosynthesis that can be fatal if untreated. Recent findings The basic biochemistry and genetics of CAH have been known for decades but continue to be refined by the discoveries of an alternative ‘backdoor’ metabolic pathway for adrenal androgen synthesis and the secretion of 11-hydroxy and 11-keto analogs of known androgens, by the elucidation of hundreds of new mutations, and by the application of high-throughput sequencing techniques to noninvasive prenatal diagno...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya Source Type: research
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