METAG
MCID: MTH082
MIFTS: 22

Methemoglobinemia and Ambiguous Genitalia (METAG)

Categories: Genetic diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Methemoglobinemia and Ambiguous Genitalia

MalaCards integrated aliases for Methemoglobinemia and Ambiguous Genitalia:

Name: Methemoglobinemia and Ambiguous Genitalia 57 72
Isolated 17,20-Lyase Deficiency, Pure 57 72
Methemoglobinemia Type Iv 72 70
Methemoglobinemia Type 4 29 6
Metag 57 72
Methemoglobinemia Due to Deficiency of Cytochrome B5, Formerly 57
Methemoglobinemia Due to Deficiency of Cytochrome B5 72
Methemoglobinemia Type Iv, Formerly 57
Methemoglobinemia, Type Iv 13
Methemoglobinemia, Type 4 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
see the more common methemoglobinemia types i and ii


HPO:

31
methemoglobinemia and ambiguous genitalia:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM® 57 250790
MeSH 44 D008708
UMLS 70 C2673427

Summaries for Methemoglobinemia and Ambiguous Genitalia

OMIM® : 57 Methemoglobinemia and ambiguous genitalia is due to isolated 17,20-lyase deficiency, defined by apparently normal 17-alpha-hydroxylase activity but severely reduced 17,20-lyase activity of the CYP17A1 enzyme (609300), which results in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. The clinical phenotype is characterized by male undermasculinization, with absent or disturbed pubertal development in both 46,XY and 46,XX individuals. Mild to severe methemoglobinemia has been reported in these patients (Idkowiak et al., 2012). Other autosomal recessive methemoglobinemias include types I and II (see 250800), caused by mutation in the CYB5R3 gene (613213). Isolated 17,20-lyase deficiency can also be caused by mutation in the CYP17A1 gene (609300), and mutation in the POR gene can manifest clinically as isolated 17,20-lyase deficiency (see 124015.0016). (250790) (Updated 05-Apr-2021)

MalaCards based summary : Methemoglobinemia and Ambiguous Genitalia, is also known as isolated 17,20-lyase deficiency, pure. An important gene associated with Methemoglobinemia and Ambiguous Genitalia is CYB5A (Cytochrome B5 Type A). Related phenotypes are micropenis and bifid scrotum

UniProtKB/Swiss-Prot : 72 Methemoglobinemia and ambiguous genitalia: An autosomal recessive disorder characterized by sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve, male undermasculinization, absent or disturbed pubertal development, decreased levels of erythrocyte cytochrome B5, and excessive amounts of methemoglobin in blood cells resulting in cyanosis and hypoxia.

Related Diseases for Methemoglobinemia and Ambiguous Genitalia

Symptoms & Phenotypes for Methemoglobinemia and Ambiguous Genitalia

Human phenotypes related to Methemoglobinemia and Ambiguous Genitalia:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 micropenis 31 HP:0000054
2 bifid scrotum 31 HP:0000048
3 hypospadias 31 HP:0000047
4 male pseudohermaphroditism 31 HP:0000037
5 ambiguous genitalia 31 HP:0000062
6 abnormality of metabolism/homeostasis 31 HP:0001939
7 cyanosis 31 HP:0000961
8 methemoglobinemia 31 HP:0012119

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Genitourinary External Genitalia Male:
micropenis
bifid scrotum
hypospadias
male pseudohermaphroditism
ambiguous genitalia
more
Skin Nails Hair Skin:
cyanosis due to methemoglobinemia

Laboratory Abnormalities:
methemoglobin concentration 12 to 19% (in 1 patient)
methemoglobinemia, mild (in some patients)

Endocrine Features:
low testosterone levels
isolated 17,20-lyase deficiency
elevated luteinizing hormone levels
subnormal response of testosterone to human chorionic gonadotropin stimulation
elevated 17-hydroxyprogesterone levels
more
Hematology:
decreased levels of erythrocyte cytochrome b5

Clinical features from OMIM®:

250790 (Updated 05-Apr-2021)

Drugs & Therapeutics for Methemoglobinemia and Ambiguous Genitalia

Search Clinical Trials , NIH Clinical Center for Methemoglobinemia and Ambiguous Genitalia

Genetic Tests for Methemoglobinemia and Ambiguous Genitalia

Genetic tests related to Methemoglobinemia and Ambiguous Genitalia:

# Genetic test Affiliating Genes
1 Methemoglobinemia Type 4 29 CYB5A

Anatomical Context for Methemoglobinemia and Ambiguous Genitalia

Publications for Methemoglobinemia and Ambiguous Genitalia

Articles related to Methemoglobinemia and Ambiguous Genitalia:

# Title Authors PMID Year
1
A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency. 57 6
22170710 2012
2
Isolated 17,20-lyase deficiency due to the cytochrome b5 mutation W27X. 6 57
20080843 2010
3
Congenital methemoglobinemia with a deficiency of cytochrome b5. 6 57
3951505 1986
4
A splicing mutation in the cytochrome b5 gene from a patient with congenital methemoglobinemia and pseudohermaphrodism. 57
8168836 1994
5
The human cytochrome b5 gene and two of its pseudogenes are located on chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively. 6
8262522 1993
6
Methemoglobinemia--sleuthing for a new cause. 57
3951508 1986
7
Catalysis of methaemoglobin reduction by erythrocyte cytochrome B5 and cytochrome B5 reductase. 57
4324110 1971
8
Assessment of a triage label system during a major incident exercise. 61
10149686 1991

Variations for Methemoglobinemia and Ambiguous Genitalia

ClinVar genetic disease variations for Methemoglobinemia and Ambiguous Genitalia:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CYB5A NM_148923.4(CYB5A):c.130-2A>G SNV Pathogenic 230 rs794728010 GRCh37: 18:71930714-71930714
GRCh38: 18:74263479-74263479
2 CYB5A NM_148923.4(CYB5A):c.81G>A (p.Trp27Ter) SNV Likely pathogenic 524200 rs1555691399 GRCh37: 18:71959030-71959030
GRCh38: 18:74291795-74291795
3 CYB5A NM_148923.4(CYB5A):c.131A>T (p.His44Leu) SNV Likely pathogenic 524201 rs1555688659 GRCh37: 18:71930711-71930711
GRCh38: 18:74263476-74263476

UniProtKB/Swiss-Prot genetic disease variations for Methemoglobinemia and Ambiguous Genitalia:

72
# Symbol AA change Variation ID SNP ID
1 CYB5A p.His44Leu VAR_080834 rs155568865

Expression for Methemoglobinemia and Ambiguous Genitalia

Search GEO for disease gene expression data for Methemoglobinemia and Ambiguous Genitalia.

Pathways for Methemoglobinemia and Ambiguous Genitalia

GO Terms for Methemoglobinemia and Ambiguous Genitalia

Sources for Methemoglobinemia and Ambiguous Genitalia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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