AH2
MCID: ADR048
MIFTS: 37

Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency (AH2)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

MalaCards integrated aliases for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

Name: Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency 58 76
3-Beta-Hsd Deficiency 58 76
Adrenal Hyperplasia 2 76 74
Congenital Adrenal Hyperplasia Due to 3-Beta-Hydroxysteroid Dehydrogenase Type Ii Deficiency 76
Congenital Adrenal Hyperplasia Due to 3-Beta-Hydroxysteroid Dehydrogenase Deficiency 60
Cah Due to 3-Beta-Hydroxysteroid Dehydrogenase Deficiency 60
3-Beta-Hydroxysteroid Dehydrogenase, Type Ii, Deficiency 13
3-Beta-Hydroxysteroid Dehydrogenase Type Ii Deficiency 76
3 Beta-Hydroxysteroid Dehydrogenase Deficiency 74
3-Beta-Hsd Deficiency; Hsdb 58
Adrenal Hyperplasia Type Ii 76
Adrenal Hyperplasia Ii 58
Ah-Ii 76
Hsdb 58
Ah2 76

Characteristics:

Orphanet epidemiological data:

60
congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

OMIM : 58 Classic 3-beta-hydroxysteroid dehydrogenase deficiency is an autosomal recessive form of CAH characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads, resulting in decreased excretion of cortisol and aldosterone and of progesterone, androgens, and estrogens by these tissues. Affected newborns exhibit signs and symptoms of glucocorticoid and mineralocorticoid deficiencies, which may be fatal if not diagnosed and treated early, especially in the severe salt-wasting form. Moreover, male newborns exhibit pseudohermaphroditism with incomplete masculinization of the external genitalia due to an impairment of androgen biosynthesis in the testis. In contrast, affected females exhibit normal sexual differentiation or partial virilization (summary by Rheaume et al., 1992). (201810)

MalaCards based summary : Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency, also known as 3-beta-hsd deficiency, is related to acth-independent macronodular adrenal hyperplasia 2 and 3-beta-hydroxysteroid dehydrogenase deficiency. An important gene associated with Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency is HSD3B2 (Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 2). The drugs Epinephrine and Racepinephrine have been mentioned in the context of this disorder. Affiliated tissues include testis, ovary and adrenal gland, and related phenotypes are hypotension and delayed skeletal maturation

UniProtKB/Swiss-Prot : 76 Adrenal hyperplasia 2: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life.

Related Diseases for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Diseases related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 acth-independent macronodular adrenal hyperplasia 2 12.7
2 3-beta-hydroxysteroid dehydrogenase deficiency 11.3
3 acth-independent macronodular adrenal hyperplasia 11.3
4 hepatitis c virus 10.3
5 helix syndrome 10.3
6 hepatitis 10.3
7 hepatitis c 10.3
8 lipoid congenital adrenal hyperplasia 10.0

Graphical network of the top 20 diseases related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:



Diseases related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency

Symptoms & Phenotypes for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Human phenotypes related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

60 33 (show top 50) (show all 66)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypotension 60 33 hallmark (90%) Very frequent (99-80%) HP:0002615
2 delayed skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0002750
3 delayed puberty 60 33 hallmark (90%) Very frequent (99-80%) HP:0000823
4 dehydration 60 33 hallmark (90%) Very frequent (99-80%) HP:0001944
5 vomiting 60 33 hallmark (90%) Very frequent (99-80%) HP:0002013
6 osteoporosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000939
7 feeding difficulties 60 33 hallmark (90%) Very frequent (99-80%) HP:0011968
8 cryptorchidism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000028
9 hyponatremia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002902
10 abnormality of the menstrual cycle 60 33 hallmark (90%) Very frequent (99-80%) HP:0000140
11 male pseudohermaphroditism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000037
12 generalized hyperpigmentation 60 33 hallmark (90%) Very frequent (99-80%) HP:0007440
13 neonatal hypoglycemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001998
14 accelerated skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0005616
15 ambiguous genitalia, male 60 33 hallmark (90%) Very frequent (99-80%) HP:0000033
16 perineal hypospadias 60 33 hallmark (90%) Very frequent (99-80%) HP:0000051
17 urogenital sinus anomaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0100779
18 renal salt wasting 60 33 hallmark (90%) Very frequent (99-80%) HP:0000127
19 increased circulating renin level 60 33 hallmark (90%) Very frequent (99-80%) HP:0000848
20 acidosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0001941
21 hyperkalemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002153
22 decreased circulating aldosterone level 60 33 hallmark (90%) Very frequent (99-80%) HP:0004319
23 increased circulating acth level 60 33 hallmark (90%) Very frequent (99-80%) HP:0003154
24 hypernatriuria 60 33 hallmark (90%) Very frequent (99-80%) HP:0012605
25 decreased circulating cortisol level 60 33 hallmark (90%) Very frequent (99-80%) HP:0008163
26 elevated circulating follicle stimulating hormone level 60 33 hallmark (90%) Very frequent (99-80%) HP:0008232
27 female external genitalia in individual with 46,xy karyotype 60 33 hallmark (90%) Very frequent (99-80%) HP:0008730
28 hypovolemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0011106
29 adrenocorticotropic hormone excess 60 33 hallmark (90%) Very frequent (99-80%) HP:0011749
30 elevated circulating luteinizing hormone level 60 33 hallmark (90%) Very frequent (99-80%) HP:0011969
31 abnormal sex determination 60 33 hallmark (90%) Very frequent (99-80%) HP:0012244
32 premature adrenarche 60 33 hallmark (90%) Very frequent (99-80%) HP:0012412
33 abnormal oral glucose tolerance 60 33 hallmark (90%) Very frequent (99-80%) HP:0004924
34 adrenogenital syndrome 60 33 hallmark (90%) Very frequent (99-80%) HP:0000840
35 androgen insufficiency 60 33 hallmark (90%) Very frequent (99-80%) HP:0008226
36 congenital adrenal hyperplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0008258
37 absence of secondary sex characteristics 60 33 frequent (33%) Frequent (79-30%) HP:0008187
38 decreased testicular size 60 33 frequent (33%) Frequent (79-30%) HP:0008734
39 gynecomastia 60 33 frequent (33%) Frequent (79-30%) HP:0000771
40 bifid scrotum 60 33 frequent (33%) Frequent (79-30%) HP:0000048
41 enlarged polycystic ovaries 60 33 frequent (33%) Frequent (79-30%) HP:0008675
42 decreased fertility in females 60 33 frequent (33%) Frequent (79-30%) HP:0000868
43 decreased fertility in males 60 33 frequent (33%) Frequent (79-30%) HP:0012041
44 insulin resistance 60 33 frequent (33%) Frequent (79-30%) HP:0000855
45 ambiguous genitalia, female 60 33 frequent (33%) Frequent (79-30%) HP:0000061
46 hyperpigmented genitalia 60 33 frequent (33%) Frequent (79-30%) HP:0030258
47 clitoral hypertrophy 33 frequent (33%) HP:0008665
48 acne 60 33 occasional (7.5%) Occasional (29-5%) HP:0001061
49 hirsutism 60 33 occasional (7.5%) Occasional (29-5%) HP:0001007
50 abnormality of the labia majora 60 33 occasional (7.5%) Occasional (29-5%) HP:0012881

Symptoms via clinical synopsis from OMIM:

58
Genitourinary External Genitalia Male:
hypospadias
ambiguous genitalia
bifid scrotum
micropenis
absent scrotum
more
Endocrine Features:
premature pubarche
elevated baseline 17-hydroxypregnenolone levels
elevated acth-stimulated 17-hydroxypregnenolone levels
elevated acth-stimulated 17-hydroxypregnenolone to cortisol ratios
elevated dehydroepiandrosterone (dhea, in some patients)

Genitourinary External Genitalia Female:
ambiguous genitalia

Genitourinary Kidneys:
salt-wasting disorder (in some patients)

Clinical features from OMIM:

201810

Drugs & Therapeutics for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Drugs for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Epinephrine Approved, Vet_approved 51-43-4 5816
2
Racepinephrine Approved 329-65-7 838
3 Androgens
4 Epinephryl borate
5 Hormones
6 Hormones, Hormone Substitutes, and Hormone Antagonists
7 Hormone Antagonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Natural History Study of Patients With Excess Androgen Enrolling by invitation NCT00250159

Search NIH Clinical Center for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency

Genetic Tests for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Anatomical Context for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

MalaCards organs/tissues related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

42
Testis, Ovary, Adrenal Gland, Bone

Publications for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Articles related to Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

(show all 14)
# Title Authors Year
1
Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. ( 18252794 )
2008
2
A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. ( 12050213 )
2002
3
A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY French-Canadians: evaluation of gonadal function after puberty. ( 10843183 )
2000
4
Characterization of two novel homozygous missense mutations involving codon 6 and 259 of type II 3beta-hydroxysteroid dehydrogenase (3betaHSD) gene causing, respectively, nonsalt-wasting and salt-wasting 3betaHSD deficiency disorder. ( 10770215 )
2000
5
New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. ( 10599696 )
1999
6
A new compound heterozygous frameshift mutation in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene causes salt-wasting 3 beta-HSD deficiency congenital adrenal hyperplasia. ( 8550766 )
1996
7
Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD. ( 7893703 )
1995
8
No evidence of mutations in the genes for type I and type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in nonclassical 3 beta HSD deficiency. ( 7989489 )
1994
9
Detection and functional characterization of the novel missense mutation Y254D in type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene of a female patient with nonsalt-losing 3 beta HSD deficiency. ( 8126127 )
1994
10
Mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia. ( 8284113 )
1993
11
Male pseudohermaphroditism caused by nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency. ( 8481355 )
1993
12
Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene. ( 1363812 )
1992
13
Congenital adrenal hyperplasia (2). ( 3295546 )
1987
14
3 beta-hydroxysteroid dehydrogenase deficiency. Follow-up study in a girl with pubertal bone age. ( 295036 )
1979

Variations for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

UniProtKB/Swiss-Prot genetic disease variations for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

76 (show all 27)
# Symbol AA change Variation ID SNP ID
1 HSD3B2 p.Glu142Lys VAR_000006 rs80358219
2 HSD3B2 p.Leu205Pro VAR_000007
3 HSD3B2 p.Ala245Pro VAR_000008
4 HSD3B2 p.Tyr253Asn VAR_000009 rs139900570
5 HSD3B2 p.Tyr254Asp VAR_000010 rs141102992
6 HSD3B2 p.Thr259Arg VAR_000011
7 HSD3B2 p.Ala10Glu VAR_010517 rs28934880
8 HSD3B2 p.Ala10Val VAR_010518 rs28934880
9 HSD3B2 p.Gly15Asp VAR_010519
10 HSD3B2 p.Ala82Thr VAR_010520 rs757033996
11 HSD3B2 p.Asn100Ser VAR_010521 rs138851794
12 HSD3B2 p.Leu108Trp VAR_010522
13 HSD3B2 p.Gly129Arg VAR_010523 rs587628683
14 HSD3B2 p.Pro155Leu VAR_010524 rs779418168
15 HSD3B2 p.Ala167Val VAR_010525 rs35486059
16 HSD3B2 p.Leu173Arg VAR_010526 rs762479018
17 HSD3B2 p.Pro186Leu VAR_010527
18 HSD3B2 p.Ser213Gly VAR_010528 rs759422374
19 HSD3B2 p.Lys216Glu VAR_010529
20 HSD3B2 p.Pro222His VAR_010530
21 HSD3B2 p.Pro222Gln VAR_010531 rs765547422
22 HSD3B2 p.Leu236Ser VAR_010533 rs35887327
23 HSD3B2 p.Thr259Met VAR_010534 rs80358221
24 HSD3B2 p.Gly294Val VAR_010535
25 HSD3B2 p.Pro222Thr VAR_015411 rs80358220
26 HSD3B2 p.Pro341Leu VAR_065665 rs121964897
27 HSD3B2 p.Ala82Pro VAR_070028

ClinVar genetic disease variations for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 HSD3B2 NM_001166120.1(HSD3B2): c.512G> A (p.Trp171Ter) single nucleotide variant Pathogenic rs80358216 GRCh37 Chromosome 1, 119964636: 119964636
2 HSD3B2 NM_001166120.1(HSD3B2): c.512G> A (p.Trp171Ter) single nucleotide variant Pathogenic rs80358216 GRCh38 Chromosome 1, 119422013: 119422013
3 HSD3B2 HSD3B2, 1-BP INS insertion Pathogenic
4 HSD3B2 NM_001166120.1(HSD3B2): c.742_743delGTinsAA (p.Val248Asn) indel Pathogenic rs121964896 GRCh37 Chromosome 1, 119964866: 119964867
5 HSD3B2 NM_001166120.1(HSD3B2): c.742_743delGTinsAA (p.Val248Asn) indel Pathogenic rs121964896 GRCh38 Chromosome 1, 119422243: 119422244
6 HSD3B2 NM_001166120.1(HSD3B2): c.29C> A (p.Ala10Glu) single nucleotide variant Pathogenic rs28934880 GRCh37 Chromosome 1, 119958071: 119958071
7 HSD3B2 NM_001166120.1(HSD3B2): c.29C> A (p.Ala10Glu) single nucleotide variant Pathogenic rs28934880 GRCh38 Chromosome 1, 119415448: 119415448
8 HSD3B2 NM_001166120.1(HSD3B2): c.1119A> C (p.Ter373Cys) single nucleotide variant Pathogenic rs80358218 GRCh37 Chromosome 1, 119965243: 119965243
9 HSD3B2 NM_001166120.1(HSD3B2): c.1119A> C (p.Ter373Cys) single nucleotide variant Pathogenic rs80358218 GRCh38 Chromosome 1, 119422620: 119422620
10 HSD3B2 NM_001166120.1(HSD3B2): c.424G> A (p.Glu142Lys) single nucleotide variant Pathogenic rs80358219 GRCh37 Chromosome 1, 119964548: 119964548
11 HSD3B2 NM_001166120.1(HSD3B2): c.424G> A (p.Glu142Lys) single nucleotide variant Pathogenic rs80358219 GRCh38 Chromosome 1, 119421925: 119421925
12 HSD3B2 NM_001166120.1(HSD3B2): c.664C> A (p.Pro222Thr) single nucleotide variant Pathogenic rs80358220 GRCh37 Chromosome 1, 119964788: 119964788
13 HSD3B2 NM_001166120.1(HSD3B2): c.664C> A (p.Pro222Thr) single nucleotide variant Pathogenic rs80358220 GRCh38 Chromosome 1, 119422165: 119422165
14 HSD3B2 NM_001166120.1(HSD3B2): c.776C> T (p.Thr259Met) single nucleotide variant Pathogenic rs80358221 GRCh37 Chromosome 1, 119964900: 119964900
15 HSD3B2 NM_001166120.1(HSD3B2): c.776C> T (p.Thr259Met) single nucleotide variant Pathogenic rs80358221 GRCh38 Chromosome 1, 119422277: 119422277
16 HSD3B2 HSD3B2, 1-BP DEL, 867G deletion Pathogenic
17 HSD3B2 NM_001166120.1(HSD3B2): c.1022C> T (p.Pro341Leu) single nucleotide variant Pathogenic rs121964897 GRCh37 Chromosome 1, 119965146: 119965146
18 HSD3B2 NM_001166120.1(HSD3B2): c.1022C> T (p.Pro341Leu) single nucleotide variant Pathogenic rs121964897 GRCh38 Chromosome 1, 119422523: 119422523
19 HSD3B2 NM_001166120.1(HSD3B2): c.1064G> A (p.Trp355Ter) single nucleotide variant Likely pathogenic rs767128094 GRCh38 Chromosome 1, 119422565: 119422565
20 HSD3B2 NM_001166120.1(HSD3B2): c.1064G> A (p.Trp355Ter) single nucleotide variant Likely pathogenic rs767128094 GRCh37 Chromosome 1, 119965188: 119965188

Expression for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Search GEO for disease gene expression data for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency.

Pathways for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

GO Terms for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

Sources for Adrenal Hyperplasia, Congenital, Due to 3-Beta-Hydroxysteroid...

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