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Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Choi JH, Kim GH, Yoo HW - Ann Pediatr Endocrinol Metab (2016)

Bottom Line: Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes.Urinary steroid analysis by gas chromatography mass spectrometry also provides qualitative and quantitative data on the excretion of steroid hormone metabolites.Molecular analysis of CYP21A2 is useful for genetic counseling, confirming diagnosis, and predicting prognoses.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
The term congenital adrenal hyperplasia (CAH) covers a group of autosomal recessive disorders caused by defects in one of the steroidogenic enzymes involved in the synthesis of cortisol or aldosterone from cholesterol in the adrenal glands. Approximately 95% of all CAH cases are caused by 21-hydroxylase deficiency encoded by the CYP21A2 gene. The disorder is categorized into classical forms, including the salt-wasting and the simple virilizing types, and nonclassical forms based on the severity of the disease. The severity of the clinical features varies according to the level of residual 21-hydroxylase activity. Newborn screening for CAH is performed in many countries to prevent salt-wasting crises in the neonatal period, to prevent male sex assignment in affected females, and to reduce long-term morbidities, such as short stature, gender confusion, and psychosexual disturbances. 17α-hydroxyprogesterone is a marker for 21-hydroxylase deficiency and is measured using a radioimmunoassay, an enzyme-linked immunosorbent assay, or a fluoroimmunoassay. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Urinary steroid analysis by gas chromatography mass spectrometry also provides qualitative and quantitative data on the excretion of steroid hormone metabolites. Molecular analysis of CYP21A2 is useful for genetic counseling, confirming diagnosis, and predicting prognoses. In conclusion, early detection using neonatal screening tests and treatment can prevent the worst outcomes of 21-hydroxylase deficiency.

No MeSH data available.


Related in: MedlinePlus

Chromosomal region of 6p21.3 containing the 21-hydroxylase genes representing the structure of RCCX module.
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Figure 1: Chromosomal region of 6p21.3 containing the 21-hydroxylase genes representing the structure of RCCX module.

Mentions: The CYP21A2 gene encodes 21-hydroxylase and requires electrons transferred from NADPH via the electron donor enzyme P450 oxidoreductase. This gene is located in the HLA class III region between the HLA-B and HLA-DR chromosome 6p21.31). This is a highly complicated region including a highly homologous pseudogene, CYP21A1P1). The functional gene (CYP21A2) and a nonfunctional pseudogene (CYP21A1P) are located closely adjacent to each other in tandem arrangement with the C4A and C4B genes encoding for the fourth component of the serum complement. Moreover, these units are located between a telomeric RP gene and a centromeric TNX gene, comprising the RCCX modules (RP-C4-CYP21-TNX) (Fig. 1)33). These genes are located in tandem and in an array (C4A, CYP21A1P, TNXA, C4B, CYP21A2, and TNXB). Genes C4A, C4B, CYP21A2, and TNXB all encode functional proteins, while CYP21A1P, TNXA, and RP2 genes are pseudogenes that do not encode proteins34).


Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Choi JH, Kim GH, Yoo HW - Ann Pediatr Endocrinol Metab (2016)

Chromosomal region of 6p21.3 containing the 21-hydroxylase genes representing the structure of RCCX module.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835555&req=5

Figure 1: Chromosomal region of 6p21.3 containing the 21-hydroxylase genes representing the structure of RCCX module.
Mentions: The CYP21A2 gene encodes 21-hydroxylase and requires electrons transferred from NADPH via the electron donor enzyme P450 oxidoreductase. This gene is located in the HLA class III region between the HLA-B and HLA-DR chromosome 6p21.31). This is a highly complicated region including a highly homologous pseudogene, CYP21A1P1). The functional gene (CYP21A2) and a nonfunctional pseudogene (CYP21A1P) are located closely adjacent to each other in tandem arrangement with the C4A and C4B genes encoding for the fourth component of the serum complement. Moreover, these units are located between a telomeric RP gene and a centromeric TNX gene, comprising the RCCX modules (RP-C4-CYP21-TNX) (Fig. 1)33). These genes are located in tandem and in an array (C4A, CYP21A1P, TNXA, C4B, CYP21A2, and TNXB). Genes C4A, C4B, CYP21A2, and TNXB all encode functional proteins, while CYP21A1P, TNXA, and RP2 genes are pseudogenes that do not encode proteins34).

Bottom Line: Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes.Urinary steroid analysis by gas chromatography mass spectrometry also provides qualitative and quantitative data on the excretion of steroid hormone metabolites.Molecular analysis of CYP21A2 is useful for genetic counseling, confirming diagnosis, and predicting prognoses.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
The term congenital adrenal hyperplasia (CAH) covers a group of autosomal recessive disorders caused by defects in one of the steroidogenic enzymes involved in the synthesis of cortisol or aldosterone from cholesterol in the adrenal glands. Approximately 95% of all CAH cases are caused by 21-hydroxylase deficiency encoded by the CYP21A2 gene. The disorder is categorized into classical forms, including the salt-wasting and the simple virilizing types, and nonclassical forms based on the severity of the disease. The severity of the clinical features varies according to the level of residual 21-hydroxylase activity. Newborn screening for CAH is performed in many countries to prevent salt-wasting crises in the neonatal period, to prevent male sex assignment in affected females, and to reduce long-term morbidities, such as short stature, gender confusion, and psychosexual disturbances. 17α-hydroxyprogesterone is a marker for 21-hydroxylase deficiency and is measured using a radioimmunoassay, an enzyme-linked immunosorbent assay, or a fluoroimmunoassay. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Urinary steroid analysis by gas chromatography mass spectrometry also provides qualitative and quantitative data on the excretion of steroid hormone metabolites. Molecular analysis of CYP21A2 is useful for genetic counseling, confirming diagnosis, and predicting prognoses. In conclusion, early detection using neonatal screening tests and treatment can prevent the worst outcomes of 21-hydroxylase deficiency.

No MeSH data available.


Related in: MedlinePlus