MCID: CLS040
MIFTS: 38

Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Categories: Bone diseases, Endocrine diseases, Metabolic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Summaries for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90794Disease definitionClassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classic 21-OHD CAH) is the most common form of congenital adrenal hyperplasia (CAH; see this term), characterized by simple virilizing or salt wasting forms that can manifest with genital ambiguity in females and with adrenal insufficiency (in both sexes), and that presents with dehydration, hypoglycemia in the neonatal period (that can be lethal if untreated), and hyperandrogenia.EpidemiologyThe prevalence is about 1/14,000.Clinical descriptionClassic 21-OHD CAH can be divided into 2 clinical groups: simple-virilizing or salt wasting (see these terms). Clinical signs of classic 21-OHD CAH are observed prenatally or at birth. Girls present with ambiguous genitalia (clitoromegaly, partially fused labia majora with rugae, common urogenital sinus) and the extent of virilization can vary from a nearly male appearance to minimal clitoromegaly. A normal uterus and various degrees of abnormal vaginal development are seen. The external genitalia in boys are normal. Salt wasting forms of CAH lead to symptoms of dehydration and hypotension in the first few weeks of life due to aldosterone deficiency. They can develop failure to thrive, hyponatremia, hyperkalemia, acidosis and hypoglycemia which can be life threatening if not treated immediately. Hyperandrogenia manifests with accelerated growth velocity and accelerated skeletal maturation (leading to short stature in adulthood), advanced bone age, premature pubarche and precocious puberty during childhood, acne and hirsutism, menstrual problems, subfertility, and metabolic disturbances and obesity during adulthood.EtiologyThe disease is caused by a mutation in the CYP21A2 gene located on chromosome 6p21.3 which controls cortisol and aldosterone production.Diagnostic methodsDiagnosis of girls with classic 21-OHD CAH is usually at birth when ambiguous genitalia are present. Fetuses can be diagnosed for CAH prenatally by measuring 17-hydroxy-progesterone (17-OHP) levels found in amniotic fluid. National systematic screening programs in most European countries diagnose cases of CAH at birth.Differential diagnosisDifferential diagnoses include other forms of CAH, polycystic ovary syndrome (PCOS, see these terms) or any diseases with androgen excess.Antenatal diagnosisPrenatal testing is available by either chorionic villus sampling (CVS) during the 10th -12th week of gestation or by amniocentesis during the 15th -18th week by measuring the enzyme activity of 17-OHP.Genetic counselingAs classic 21-OHD CAH follows an autosomal recessive pattern of inheritance, genetic counseling is possible.Management and treatmentPrenatal treatment with dexamethasone can be administered to female fetuses at risk of developing classic CAH. When administered before the 9th week of gestation, it prevents the excessive androgen production responsible for genital ambiguity in females. If diagnosed after birth, vaginoplasty surgery is usually performed on girls in the first year of life. Lifelong hormone replacement therapy is needed to treat adrenal insufficiency and to decrease elevated androgen hormone levels in order to allow for normal growth and puberty. Hydrocortisone is usually given to children as glucocorticoid (GC) replacement therapy (10-15mg/m2/day divided into 2 or 3 doses) and 9alpha-fludrocortisone for mineralocorticoid (MC) replacement. Dosage is monitored and modified during times of stress. There is a risk of developing acute adrenal insufficiency (see this term) and other complications due to chronic hyperandrogenemia. Excessive treatment with GC causes cushingoid features, and excess MC causes hypertension. Regular follow-up by a multidisciplinary team, including pediatric endocrinologists, surgeons, gynecologists, psychologists, is important.PrognosisWith proper treatment patients have a normal life expectancy.Visit the Orphanet disease page for more resources.

MalaCards based summary : Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency, also known as classic 21-ohd cah, is related to lipoid congenital adrenal hyperplasia and hyperandrogenism. An important gene associated with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency is CYP21A2 (Cytochrome P450 Family 21 Subfamily A Member 2), and among its related pathways/superpathways are Cushing syndrome and Peptide hormone metabolism. Affiliated tissues include bone, ovary and testes, and related phenotypes are obesity and hypertension

Related Diseases for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Diseases related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 42)
# Related Disease Score Top Affiliating Genes
1 lipoid congenital adrenal hyperplasia 31.5 CYP21A2 POMC
2 hyperandrogenism 30.4 CYP21A2 POMC
3 polycystic ovary syndrome 30.2 CYP21A2 LEP
4 non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 13.0
5 classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form 12.7
6 classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form 12.7
7 adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 12.0
8 acute adrenal insufficiency 10.1 CYP21A2 POMC
9 cytochrome p450 oxidoreductase deficiency 10.1 CYP21A2 POMC
10 testicular leydig cell tumor 10.0 CYP21A2 POMC
11 adrenal cortical hypofunction 10.0 CYP21A2 POMC
12 steroid inherited metabolic disorder 10.0 CYP21A2 POMC
13 sex differentiation disease 10.0 CYP21A2 POMC
14 adrenal cortical adenoma 10.0 CYP21A2 POMC
15 adenoma 10.0 CYP21A2 POMC
16 pituitary-dependent cushing's disease 10.0 CYP21A2 POMC
17 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 10.0 CYP21A2 POMC
18 adrenal rest tumor 10.0 CYP21A2 POMC
19 hypoadrenocorticism, familial 10.0 CYP21A2 POMC
20 cortisone reductase deficiency 10.0 CYP21A2 POMC
21 adrenal adenoma 10.0 CYP21A2 POMC
22 sick building syndrome 10.0 LEP POMC
23 inherited metabolic disorder 10.0 CYP21A2 LEP
24 adrenal carcinoma 10.0 CYP21A2 POMC
25 hypercholesterolemia, autosomal recessive 10.0 LEP POMC
26 pancreas disease 10.0 LEP POMC
27 amenorrhea 10.0 LEP POMC
28 eating disorder 10.0 LEP POMC
29 overnutrition 9.9 LEP POMC
30 glucose metabolism disease 9.9 LEP POMC
31 adrenocortical carcinoma, hereditary 9.9 CYP21A2 POMC
32 acquired metabolic disease 9.9 LEP POMC
33 autism 6 9.9 LEP LEPQTL1
34 obesity-hypoventilation syndrome 9.9 LEP LEPQTL1
35 berardinelli-seip congenital lipodystrophy 9.9 LEP LEPQTL1
36 fetal macrosomia 9.9 LEP LEPQTL1
37 conn's syndrome 9.9 CYP21A2 POMC
38 glucose intolerance 9.8 LEP LEPQTL1
39 hypothyroidism 9.8 LEP POMC
40 anorexia nervosa 9.7 LEP LEPQTL1 POMC
41 prader-willi syndrome 9.7 LEP LEPQTL1 POMC
42 body mass index quantitative trait locus 11 9.5 CYP21A2 LEP LEPQTL1 POMC

Graphical network of the top 20 diseases related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency:



Diseases related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Symptoms & Phenotypes for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Human phenotypes related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency:

32 (show top 50) (show all 57)
# Description HPO Frequency HPO Source Accession
1 obesity 32 frequent (33%) HP:0001513
2 hypertension 32 frequent (33%) HP:0000822
3 intellectual disability 32 occasional (7.5%) HP:0001249
4 failure to thrive 32 occasional (7.5%) HP:0001508
5 hypotension 32 hallmark (90%) HP:0002615
6 short stature 32 hallmark (90%) HP:0004322
7 dehydration 32 hallmark (90%) HP:0001944
8 vomiting 32 hallmark (90%) HP:0002013
9 osteoporosis 32 hallmark (90%) HP:0000939
10 feeding difficulties 32 hallmark (90%) HP:0011968
11 acne 32 frequent (33%) HP:0001061
12 aggressive behavior 32 occasional (7.5%) HP:0000718
13 hyponatremia 32 hallmark (90%) HP:0002902
14 adrenocortical adenoma 32 occasional (7.5%) HP:0008256
15 gynecomastia 32 occasional (7.5%) HP:0000771
16 long penis 32 frequent (33%) HP:0000040
17 female pseudohermaphroditism 32 occasional (7.5%) HP:0010458
18 enlarged polycystic ovaries 32 hallmark (90%) HP:0008675
19 generalized hyperpigmentation 32 frequent (33%) HP:0007440
20 abnormal spermatogenesis 32 frequent (33%) HP:0008669
21 neonatal hypoglycemia 32 hallmark (90%) HP:0001998
22 urogenital sinus anomaly 32 frequent (33%) HP:0100779
23 renal salt wasting 32 occasional (7.5%) HP:0000127
24 increased circulating renin level 32 hallmark (90%) HP:0000848
25 acidosis 32 hallmark (90%) HP:0001941
26 hyperkalemia 32 hallmark (90%) HP:0002153
27 decreased circulating aldosterone level 32 hallmark (90%) HP:0004319
28 increased circulating acth level 32 hallmark (90%) HP:0003154
29 hypernatriuria 32 hallmark (90%) HP:0012605
30 decreased circulating cortisol level 32 hallmark (90%) HP:0008163
31 hypovolemia 32 hallmark (90%) HP:0011106
32 adrenocorticotropic hormone excess 32 frequent (33%) HP:0011749
33 decreased fertility in females 32 frequent (33%) HP:0000868
34 decreased fertility in males 32 frequent (33%) HP:0012041
35 insulin resistance 32 occasional (7.5%) HP:0000855
36 premature adrenarche 32 hallmark (90%) HP:0012412
37 hirsutism 32 hallmark (90%) HP:0001007
38 menstrual irregularities 32 hallmark (90%) HP:0000858
39 abnormality of circulating leptin level 32 frequent (33%) HP:0004361
40 ambiguous genitalia, female 32 frequent (33%) HP:0000061
41 abnormal scrotal rugation 32 frequent (33%) HP:0012856
42 fused labia minora 32 frequent (33%) HP:0000063
43 clitoral hypertrophy 32 frequent (33%) HP:0008665
44 increased circulating androgen level 32 hallmark (90%) HP:0030348
45 hyperpigmented genitalia 32 frequent (33%) HP:0030258
46 abnormal oral glucose tolerance 32 frequent (33%) HP:0004924
47 maternal virilization in pregnancy 32 occasional (7.5%) HP:0008072
48 accelerated bone age after puberty 32 hallmark (90%) HP:0002805
49 adrenogenital syndrome 32 hallmark (90%) HP:0000840
50 congenital adrenal hyperplasia 32 hallmark (90%) HP:0008258

GenomeRNAi Phenotypes related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 9.32 POMC
2 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.32 POMC
3 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.32 LEP
4 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.32 LEP POMC
5 Increased shRNA abundance (Z-score > 2) GR00366-A-199 9.32 LEP
6 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.32 POMC
7 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.32 POMC
8 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.32 POMC
9 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.32 POMC

Drugs & Therapeutics for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Search Clinical Trials , NIH Clinical Center for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Genetic Tests for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Anatomical Context for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

MalaCards organs/tissues related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency:

41
Bone, Ovary, Testes, Uterus, Adrenal Gland, Pituitary, Pancreas

Publications for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Articles related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency:

(show all 16)
# Title Authors Year
1
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency - the next disease included in the neonatal screening program in Poland. ( 30056407 )
2018
2
The prevalence of non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Russian women with hyperandrogenism. ( 28669219 )
2017
3
Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. ( 28582566 )
2017
4
Non-Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency that Developed into Symptomatic Severe Hyponatremia. ( 25986269 )
2015
5
Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase-Deficiency: 13 Years of Neonatal Screening and Follow-up in Bavaria. ( 26090996 )
2015
6
Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency followed from birth to 4A years of age. ( 24818525 )
2014
7
A case of recurrent labial adhesions in a 15-month-old child with asymptomatic non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 23426836 )
2012
8
Adrenarche and puberty in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 22123283 )
2011
9
Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 20395657 )
2010
10
Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency can achieve their target height: the Leipzig experience. ( 18493149 )
2008
11
[Comparative study of prednisolone versus hydrocortisone acetate for treatment of patients with the classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. ( 18345402 )
2008
12
Growth in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 18174719 )
2007
13
Cardiovascular risk factors and ultrasound evaluation of intima-media thickness at common carotids, carotid bulbs, and femoral and abdominal aorta arteries in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 17200174 )
2007
14
Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 16396852 )
2006
15
Absence of exercise-induced leptin suppression associated with insufficient epinephrine reserve in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 16636975 )
2006
16
Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. ( 10084573 )
1999

Variations for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

ClinVar genetic disease variations for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CYP21A2 NM_000500.7(CYP21A2): c.518T> A (p.Ile173Asn) single nucleotide variant Pathogenic rs6475 GRCh37 Chromosome 6, 32007203: 32007203
2 CYP21A2 NM_000500.7(CYP21A2): c.518T> A (p.Ile173Asn) single nucleotide variant Pathogenic rs6475 GRCh38 Chromosome 6, 32039426: 32039426

Expression for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Search GEO for disease gene expression data for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Pathways for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

GO Terms for Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase...

Biological processes related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 glucose homeostasis GO:0042593 8.96 LEP POMC
2 regulation of blood pressure GO:0008217 8.62 LEP POMC

Molecular functions related to Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.62 LEP POMC

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