DISPORD
MCID: DSR012
MIFTS: 37

Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency (DISPORD)

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

Aliases & Classifications for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

MalaCards integrated aliases for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

Name: Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency 56 73 29 6
Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase 56 52 36 13
Disordered Steroidogenesis Due to Por Deficiency 56 52 73
Por Deficiency 52 58 73
Congenital Adrenal Hyperplasia Due to Apparent Combined P450c17 and P450c21 Deficiency 73 29
Adrenal Hyperplasia, Congenital, Due to Cytochrome P450 Oxidoreductase Deficiency 56 52
Congenital Adrenal Hyperplasia Due to Cytochrome P450 Oxidoreductase Deficiency 52 58
Congenital Adrenal Hyperplasia Due to Cytochrome Por Deficiency 52 58
Pord 52 58
Adrenal Hyperplasia Congenital Due to Cytochrome P450 Oxidoreductase Deficiency 73
Steroidogenesis, Disordered, Due to Cytochrome P450 Oxidoreductase Deficiency 39
Antley-Bixler Syndrome with Disordered Steroidogenesis 71
Cytochrome P450 Oxidoreductase Deficiency 73
Dispord 73

Characteristics:

Orphanet epidemiological data:

58
congenital adrenal hyperplasia due to cytochrome p450 oxidoreductase deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal;

HPO:

31
disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare gynaecological and obstetric diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 95699 Definition Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency is a unique form of congenital adrenal hyperplasia (CAH; see this term) characterized by glucocorticoid deficiency, severe sexual ambiguity in both sexes and skeletal (especially craniofacial) malformations. Epidemiology It has an annual incidence of 1/100,000-200,000 live births. Clinical description Prenatal androgen excess is responsible for severe virilization of external genitalia in girls and undervirilization in boys manifesting as a micropenis to severe perineoscrotal hypospadias. Craniofacial malformations observed include large domed forehead, flat nose, midface hypoplasia with proptosis and dysplastic ears and other features similar to those seen in Antley-Bixler syndrome (see this term). Etiology This form of CAH is caused by a mutation in the POR gene located on chromosome 7 q11.2. Genetic counseling The disease follows an autosomal recessive pattern of inheritance. Visit the Orphanet disease page for more resources.

MalaCards based summary : Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency, also known as disordered steroidogenesis due to cytochrome p450 oxidoreductase, is related to cytochrome p450 oxidoreductase deficiency and aromatase deficiency. An important gene associated with Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency is POR (Cytochrome P450 Oxidoreductase). Affiliated tissues include bone, ovary and adrenal gland, and related phenotypes are delayed skeletal maturation and delayed puberty

OMIM : 56 This rare variant of congenital adrenal hyperplasia, caused by mutations in the POR gene, results in apparent combined deficiency of P450C17 (609300) and P450C21 (613815) and accumulation of steroid metabolites. The most striking phenotypic feature is that affected girls are born with ambiguous genitalia, indicating intrauterine androgen excess. After birth, however, virilization does not progress and amounts of circulating androgens are low or normal. Affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, sometimes suggesting the pattern seen in patients with Antley-Bixler syndrome (see 207410) (summary by Arlt et al., 2004). (613571)

KEGG : 36 Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder with a broad phenotypic spectrum including skeletal malformations resembling the Antley-Bixler syndrome phenotype and abnormalities in adrenal steroid biosynthesis resulting in congenital adrenal hyperplasia.

UniProtKB/Swiss-Prot : 73 Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency: A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.

Related Diseases for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

Graphical network of the top 20 diseases related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:



Diseases related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency

Symptoms & Phenotypes for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

Human phenotypes related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

58 31 (show top 50) (show all 66)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
2 delayed puberty 58 31 hallmark (90%) Very frequent (99-80%) HP:0000823
3 osteoporosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000939
4 absence of secondary sex characteristics 58 31 hallmark (90%) Very frequent (99-80%) HP:0008187
5 decreased serum testosterone level 58 31 hallmark (90%) Very frequent (99-80%) HP:0040171
6 premature adrenarche 58 31 hallmark (90%) Very frequent (99-80%) HP:0012412
7 abnormality of the menstrual cycle 58 31 hallmark (90%) Very frequent (99-80%) HP:0000140
8 tall stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0000098
9 enlarged polycystic ovaries 58 31 hallmark (90%) Very frequent (99-80%) HP:0008675
10 accelerated skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0005616
11 increased serum testosterone level 58 31 hallmark (90%) Very frequent (99-80%) HP:0030088
12 female external genitalia in individual with 46,xy karyotype 58 31 hallmark (90%) Very frequent (99-80%) HP:0008730
13 adrenocorticotropic hormone excess 58 31 hallmark (90%) Very frequent (99-80%) HP:0011749
14 decreased serum estradiol 58 31 hallmark (90%) Very frequent (99-80%) HP:0008214
15 ambiguous genitalia, female 58 31 hallmark (90%) Very frequent (99-80%) HP:0000061
16 hyperpigmented genitalia 58 31 hallmark (90%) Very frequent (99-80%) HP:0030258
17 abnormality of the labia majora 58 31 hallmark (90%) Very frequent (99-80%) HP:0012881
18 maternal virilization in pregnancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008072
19 adrenogenital syndrome 58 31 hallmark (90%) Very frequent (99-80%) HP:0000840
20 congenital adrenal hyperplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008258
21 clitoral hypertrophy 31 hallmark (90%) HP:0008665
22 low-set ears 58 31 frequent (33%) Frequent (79-30%) HP:0000369
23 clinodactyly 58 31 frequent (33%) Frequent (79-30%) HP:0030084
24 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
25 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
26 craniosynostosis 58 31 frequent (33%) Frequent (79-30%) HP:0001363
27 flexion contracture 58 31 frequent (33%) Frequent (79-30%) HP:0001371
28 midface retrusion 58 31 frequent (33%) Frequent (79-30%) HP:0011800
29 decreased testicular size 58 31 frequent (33%) Frequent (79-30%) HP:0008734
30 micropenis 58 31 frequent (33%) Frequent (79-30%) HP:0000054
31 choanal atresia 58 31 frequent (33%) Frequent (79-30%) HP:0000453
32 bifid scrotum 58 31 frequent (33%) Frequent (79-30%) HP:0000048
33 arachnodactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001166
34 generalized hyperpigmentation 58 31 frequent (33%) Frequent (79-30%) HP:0007440
35 male pseudohermaphroditism 58 31 frequent (33%) Frequent (79-30%) HP:0000037
36 ambiguous genitalia, male 58 31 frequent (33%) Frequent (79-30%) HP:0000033
37 perineal hypospadias 58 31 frequent (33%) Frequent (79-30%) HP:0000051
38 urogenital sinus anomaly 58 31 frequent (33%) Frequent (79-30%) HP:0100779
39 choanal stenosis 58 31 frequent (33%) Frequent (79-30%) HP:0000452
40 increased circulating acth level 58 31 frequent (33%) Frequent (79-30%) HP:0003154
41 decreased circulating cortisol level 58 31 frequent (33%) Frequent (79-30%) HP:0008163
42 abnormal sex determination 58 31 frequent (33%) Frequent (79-30%) HP:0012244
43 decreased fertility in females 58 31 frequent (33%) Frequent (79-30%) HP:0000868
44 decreased fertility in males 58 31 frequent (33%) Frequent (79-30%) HP:0012041
45 female sexual dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0030014
46 hypoplasia of the vagina 58 31 frequent (33%) Frequent (79-30%) HP:0008726
47 androgen insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0008226
48 ectopic adrenal gland 58 31 frequent (33%) Frequent (79-30%) HP:0011742
49 pear-shaped nose 58 31 frequent (33%) Frequent (79-30%) HP:0000447
50 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822

Clinical features from OMIM:

613571

Drugs & Therapeutics for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

Search Clinical Trials , NIH Clinical Center for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency

Genetic Tests for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

Genetic tests related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

# Genetic test Affiliating Genes
1 Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency 29 POR
2 Congenital Adrenal Hyperplasia Due to Apparent Combined P450c17 and P450c21 Deficiency 29

Anatomical Context for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

MalaCards organs/tissues related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

40
Bone, Ovary, Adrenal Gland

Publications for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

Articles related to Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

(show all 48)
# Title Authors PMID Year
1
Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency. 61 56 6
18559916 2008
2
Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. 61 56 6
15793702 2005
3
Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. 56 6
15220035 2004
4
Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. 56 6
14758361 2004
5
A single amino acid substitution in the putative redox partner-binding site of P450c17 as cause of isolated 17,20-lyase deficiency. 56 6
9360545 1997
6
Linking Antley-Bixler syndrome and congenital adrenal hyperplasia: a novel case of P450 oxidoreductase deficiency. 56
16906539 2006
7
POR R457H is a global founder mutation causing Antley-Bixler syndrome with autosomal recessive trait. 6
16470797 2006
8
Cytochrome P450 Oxidoreductase Deficiency 6
20301592 2005
9
Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. 6
15483095 2005
10
Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): a disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley-Bixler syndrome phenotype. 56
15316970 2004
11
Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia. 6
12116245 2002
12
Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia. 56
2932643 1985
13
Signal recognition particle is required for co-translational insertion of cytochrome P-450 into microsomal membranes. 56
6587354 1984
14
Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 activities caused by genetic variations in cytochrome P450 oxidoreductase. 61
31128914 2019
15
In vitro fertilization-frozen embryo transfer in a patient with cytochrome P450 oxidoreductase deficiency: a case report. 61
29069987 2018
16
Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency. 61
29289577 2018
17
P450 Oxidoreductase Deficiency: Loss of Activity Caused by Protein Instability From a Novel L374H Mutation. 61
27603900 2016
18
Instability of the Human Cytochrome P450 Reductase A287P Variant Is the Major Contributor to Its Antley-Bixler Syndrome-like Phenotype. 61
27496950 2016
19
Delayed diagnosis of disorder of sex development (DSD) due to P450 oxidoreductase (POR) deficiency. 61
27376429 2016
20
P450 oxidoreductase deficiency with maternal virilization during pregnancy. 61
29944250 2016
21
Prenatal Diagnosis of Antley-Bixler Syndrome and POR Deficiency. 61
26670660 2015
22
Electron transfer by human wild-type and A287P mutant P450 oxidoreductase assessed by transient kinetics: functional basis of P450 oxidoreductase deficiency. 61
25728647 2015
23
Cytochrome P450 oxidoreductase deficiency: rare congenital disorder leading to skeletal malformations and steroidogenic defects. 61
25294558 2014
24
NADPH P450 oxidoreductase: structure, function, and pathology of diseases. 61
23353702 2013
25
P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations. 61
23092891 2012
26
Proximal promoter of the cytochrome P450 oxidoreductase gene: identification of microdeletions involving the untranslated exon 1 and critical function of the SP1 binding sites. 61
21900384 2011
27
A rare cause of congenital adrenal hyperplasia: Antley-Bixler syndrome due to POR deficiency. 61
21868813 2011
28
Clinical and biochemical consequences of p450 oxidoreductase deficiency. 61
21164260 2011
29
Impaired hepatic drug and steroid metabolism in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. 61
20844025 2010
30
Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase. 61
20732302 2010
31
Anorectal and urinary anomalies and aberrant retinoic acid metabolism in cytochrome P450 oxidoreductase deficiency. 61
20409737 2010
32
Concomitant mutations in the P450 oxidoreductase and androgen receptor genes presenting with 46,XY disordered sex development and androgenization at adrenarche. 61
20410220 2010
33
Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. 61
19884324 2010
34
Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients. 61
19837910 2009
35
A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene. 61
18853185 2009
36
Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously. 61
19621255 2009
37
Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35 Japanese patients. 61
19258400 2009
38
Genetic variation in human P450 oxidoreductase. 61
18930113 2009
39
Genetic and clinical features of p450 oxidoreductase deficiency. 61
18259105 2008
40
P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia. 61
18493134 2008
41
[Antley-Bixler syndrome or POR deficiency?]. 61
18630181 2008
42
P450 oxidoreductase deficiency and Antley-Bixler syndrome. 61
17960482 2007
43
Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase. 61
17595315 2007
44
Differential inhibition of CYP17A1 and CYP21A2 activities by the P450 oxidoreductase mutant A287P. 61
17505056 2007
45
Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. 61
17389698 2007
46
Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: diagnostic value of urine steroid hormone analysis. 61
16439592 2006
47
P450 oxidoreductase deficiency: a new disorder of steroidogenesis. 61
16467261 2005
48
P450 oxidoreductase deficiency: a new disorder of steroidogenesis affecting all microsomal P450 enzymes. 61
15666840 2004

Variations for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase...

ClinVar genetic disease variations for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

6 (show all 13) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 POR NM_000941.3(POR):c.859G>C (p.Ala287Pro)SNV Pathogenic 16902 rs121912974 7:75612866-75612866 7:75983548-75983548
2 POR NM_000941.3(POR):c.1706G>A (p.Cys569Tyr)SNV Pathogenic 16903 rs28931607 7:75615277-75615277 7:75985959-75985959
3 POR NM_000941.3(POR):c.1822G>T (p.Val608Phe)SNV Pathogenic 16904 rs72552772 7:75615483-75615483 7:75986165-75986165
4 POR NM_000941.3(POR):c.541T>G (p.Tyr181Asp)SNV Pathogenic 16906 rs72552771 7:75610390-75610390 7:75981072-75981072
5 POR NM_000941.3(POR):c.1615G>A (p.Gly539Arg)SNV Pathogenic 16915 rs121912976 7:75615113-75615113 7:75985795-75985795
6 POR NM_000941.3(POR):c.1571_1619dup (p.Ala541fs)duplication Pathogenic 580516 rs1563435458 7:75615068-75615069 7:75985750-75985751
7 POR NM_000941.3(POR):c.1370G>A (p.Arg457His)SNV Pathogenic/Likely pathogenic 16907 rs28931608 7:75614497-75614497 7:75985179-75985179
8 POR NM_000941.3(POR):c.1363del (p.Gln455fs)deletion Likely pathogenic 632505 rs781805159 7:75614490-75614490 7:75985172-75985172
9 POR NM_000941.3(POR):c.188+2T>CSNV Likely pathogenic 576622 rs936203749 7:75583500-75583500 7:75954182-75954182
10 POR NM_000941.3(POR):c.1660C>T (p.Arg554Ter)SNV Uncertain significance 632506 rs782336856 7:75615158-75615158 7:75985840-75985840
11 POR NM_000941.3(POR):c.214T>C (p.Phe72Leu)SNV Uncertain significance 469120 rs782107314 7:75601756-75601756 7:75972438-75972438
12 POR NM_000941.3(POR):c.513C>G (p.Phe171Leu)SNV Uncertain significance 572685 rs372715546 7:75609803-75609803 7:75980485-75980485
13 POR NM_000941.3(POR):c.1384G>C (p.Ala462Pro)SNV Uncertain significance 576473 rs72557936 7:75614511-75614511 7:75985193-75985193

UniProtKB/Swiss-Prot genetic disease variations for Disordered Steroidogenesis Due to Cytochrome P450 Oxidoreductase Deficiency:

73
# Symbol AA change Variation ID SNP ID
1 POR p.Tyr178Asp VAR_021154
2 POR p.Ala284Pro VAR_021155
3 POR p.Arg454His VAR_021156
4 POR p.Cys566Tyr VAR_021158 rs72552772
5 POR p.Val605Phe VAR_021160

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