METHB-CYB5R3
MCID: MTH026
MIFTS: 34

Methemoglobinemia Due to Deficiency of Methemoglobin Reductase (METHB-CYB5R3)

Categories: Blood diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

MalaCards integrated aliases for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

Name: Methemoglobinemia Due to Deficiency of Methemoglobin Reductase 58 54 76
Methemoglobinemia, Type I 58 30 13 6
Nadh-Dependent Methemoglobin Reductase Deficiency 58 54 76
Nadh-Cytochrome B5 Reductase Deficiency 58 26 76
Nadh Cytochrome B5 Reductase Deficiency 54 74
Deficiency of Cytochrome-B5 Reductase 26 30
Methemoglobinemia Type 2 30 6
Diaphorase Deficiency 54 26
Congenital Methemoglobinemia Due to Nadh-Cytochrome B5 Reductase 3 Deficiency 26
Chronic Familial Methemoglobin Reductase Deficiency 26
Methemoglobinemia, Congenital, Autosomal Recessive 58
Congenital Nadh-Methemoglobin Reductase Deficiency 26
Autosomal Recessive Congenital Methemoglobinemia 26
Methemoglobinemia Congenital Autosomal Recessive 76
Nadh-Cytochrome B5 Reductase Deficiency Type Ii 76
Nadh-Cytochrome B5 Reductase Deficiency, Type I 30
Nadh-Cytochrome B5 Reductase Deficiency Type I 76
Nadh Methemoglobin Reductase Deficiency 54
Autosomal Recessive Methemoglobinemia 54
Cytochrome B5 Reductase Deficiency 26
Methemoglobinemia Cyb5r3-Related 76
Methemoglobinemia, Type Ii 58
Nadh Diaphorase Deficiency 54
Methemoglobinemia Type Ii 76
Methemoglobinemia Type I 76
Nadh-Cyb5r Deficiency 26
Methb-Cyb5r3 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
most common form of congenital methemoglobinemia
two clinical forms - type i (deficiency of b5r is isolated to erythrocytes) and type ii (deficiency of b5r in all cell types)
type ii is progressive and leads to shortened lifespan
type i b5r endemic in athabascan indians, navajo indians, and yakutsk natives of siberia
heterozygotes at risk of developing acute, symptomatic methemoglobinemia after exposure to exogenous, methemoglobin-inducing agents


HPO:

33
methemoglobinemia due to deficiency of methemoglobin reductase:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

OMIM : 58 Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008). There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979). (250800)

MalaCards based summary : Methemoglobinemia Due to Deficiency of Methemoglobin Reductase, also known as methemoglobinemia, type i, is related to pyruvate dehydrogenase e3-binding protein deficiency and dihydrolipoamide dehydrogenase deficiency, and has symptoms including seizures, ataxia and headache. An important gene associated with Methemoglobinemia Due to Deficiency of Methemoglobin Reductase is CYB5R3 (Cytochrome B5 Reductase 3). Affiliated tissues include skin, and related phenotypes are intellectual disability and global developmental delay

Genetics Home Reference : 26 Autosomal recessive congenital methemoglobinemia is an inherited condition that mainly affects the function of red blood cells. Specifically, it alters a molecule within these cells called hemoglobin. Hemoglobin carries oxygen to cells and tissues throughout the body. In people with autosomal recessive congenital methemoglobinemia, some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, which is unable to deliver oxygen to the body's tissues. As a result, tissues in the body become oxygen deprived, leading to a bluish appearance of the skin, lips, and nails (cyanosis).

UniProtKB/Swiss-Prot : 76 Methemoglobinemia CYB5R3-related: A form of methemoglobinemia, a hematologic disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2 methemoglobinemia is associated with mental deficiency and other neurologic symptoms.

Related Diseases for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Diseases related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pyruvate dehydrogenase e3-binding protein deficiency 11.7
2 dihydrolipoamide dehydrogenase deficiency 11.7
3 maple syrup urine disease 11.7
4 methemoglobinemia and ambiguous genitalia 11.1
5 methemoglobinemia 10.6
6 methemoglobin reductase deficiency 10.5
7 congenital methemoglobinemia 10.5
8 hereditary methemoglobinemia 10.5

Graphical network of the top 20 diseases related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:



Diseases related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Symptoms & Phenotypes for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Human phenotypes related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

33 (show all 12)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 33 HP:0001249
2 global developmental delay 33 HP:0001263
3 microcephaly 33 HP:0000252
4 hypertonia 33 HP:0001276
5 strabismus 33 HP:0000486
6 growth delay 33 HP:0001510
7 headache 33 HP:0002315
8 polycythemia 33 HP:0001901
9 cyanosis 33 HP:0000961
10 exertional dyspnea 33 HP:0002875
11 opisthotonus 33 HP:0002179
12 methemoglobinemia 33 HP:0012119

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
headache
mental retardation (type i)
developmental delay (type ii)
opisthotonos (type ii)
hypertonia (type ii)
more
Skin Nails Hair Skin:
cyanosis

Head And Neck Head:
microcephaly (type ii)

Respiratory:
dyspnea, exertional

Hematology:
polycythemia
type i - methemoglobin concentration 10-35%

Growth Other:
growth retardation

Head And Neck Eyes:
strabismus (type ii)

Laboratory Abnormalities:
nadh-cytochrome b(5) reductase deficiency

Clinical features from OMIM:

250800

UMLS symptoms related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:


seizures, ataxia, headache, lethargy, cyanosis, dyspnea on exertion

Drugs & Therapeutics for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Search Clinical Trials , NIH Clinical Center for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Genetic Tests for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Genetic tests related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

# Genetic test Affiliating Genes
1 Methemoglobinemia Type 2 30
2 Methemoglobinemia, Type I 30
3 Deficiency of Cytochrome-B5 Reductase 30 CYB5R3
4 Nadh-Cytochrome B5 Reductase Deficiency, Type I 30

Anatomical Context for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

MalaCards organs/tissues related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

42
Skin

Publications for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Articles related to Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

(show all 22)
# Title Authors Year
1
Novel mutation (R192C) in CYB5R3 gene causing NADH-cytochrome b5 reductase deficiency in eight Indian patients associated with autosomal recessive congenital methemoglobinemia type-I. ( 29482478 )
2018
2
Recessive congenital methaemoglobinaemia: cytochrome b(5) reductase deficiency. ( 18318771 )
2008
3
Heterogeneity of the molecular biology of methemoglobinemia: a study of eight consecutive patients. ( 15921385 )
2005
4
Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase. ( 15953014 )
2005
5
[A search for mutations in the DIA1 gene in case of hereditary methemoglobinemia type I in the iakut population]. ( 12884529 )
2003
6
Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase. ( 12393396 )
2002
7
Seven new mutations in the nicotinamide adenine dinucleotide reduced-cytochrome b(5) reductase gene leading to methemoglobinemia type I. ( 11159544 )
2001
8
A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. ( 10807796 )
2000
9
A compound heterozygote in the NADH-cytochrome b5 reductase gene from a Chinese patient with hereditary methemoglobinemia type I. ( 10979206 )
2000
10
A case of methemoglobinemia type II due to NADH-cytochrome b5 reductase deficiency: determination of the molecular basis. ( 10874300 )
2000
11
Identification of a novel point mutation (Leu72Pro) in the NADH-cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I. ( 9695975 )
1998
12
Recessive congenital methaemoglobinaemia type II a new mutation which causes incorrect splicing in the NADH-cytochrome b5 reductase gene. ( 9266404 )
1997
13
Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II. ( 7718898 )
1995
14
A novel point mutation in a 3' splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia. ( 7668255 )
1995
15
An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme. ( 8119939 )
1994
16
Analysis of mutant NADH-cytochrome b5 reductase: apparent "type III" methemoglobinemia can be explained as type I with an unstable reductase. ( 8427971 )
1993
17
Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). ( 1400360 )
1992
18
Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency. ( 1707593 )
1991
19
Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase. ( 1898726 )
1991
20
Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type. ( 2107882 )
1990
21
Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders. ( 4063522 )
1985
22
The reduction of methaemoglobin in red blood cells and studies on the cause of idiopathic methaemoglobinaemia. ( 16748235 )
1948

Variations for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

UniProtKB/Swiss-Prot genetic disease variations for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

76
# Symbol AA change Variation ID SNP ID
1 CYB5R3 p.Arg58Gln VAR_004619 rs121965007
2 CYB5R3 p.Val106Met VAR_004620 rs121965009
3 CYB5R3 p.Ser128Pro VAR_004621 rs121965006
4 CYB5R3 p.Leu149Pro VAR_004622 rs121965008
5 CYB5R3 p.Leu73Pro VAR_010750 rs121965013
6 CYB5R3 p.Ala179Val VAR_010752 rs201232518
7 CYB5R3 p.Cys204Arg VAR_010753 rs121965011
8 CYB5R3 p.Cys204Tyr VAR_010754 rs121965015
9 CYB5R3 p.Gly292Asp VAR_037316 rs121965016

ClinVar genetic disease variations for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase:

6 (show all 36)
# Gene Variation Type Significance SNP ID Assembly Location
1 CYB5R3 NM_000398.6(CYB5R3): c.655C> T (p.Arg219Ter) single nucleotide variant Pathogenic rs121965010 GRCh38 Chromosome 22, 42623867: 42623867
2 CYB5R3 NM_000398.6(CYB5R3): c.382T> C (p.Ser128Pro) single nucleotide variant Pathogenic rs121965006 GRCh37 Chromosome 22, 43024239: 43024239
3 CYB5R3 NM_000398.6(CYB5R3): c.382T> C (p.Ser128Pro) single nucleotide variant Pathogenic rs121965006 GRCh38 Chromosome 22, 42628233: 42628233
4 CYB5R3 NM_000398.6(CYB5R3): c.173G> A (p.Arg58Gln) single nucleotide variant Pathogenic rs121965007 GRCh37 Chromosome 22, 43027437: 43027437
5 CYB5R3 NM_000398.6(CYB5R3): c.173G> A (p.Arg58Gln) single nucleotide variant Pathogenic rs121965007 GRCh38 Chromosome 22, 42631431: 42631431
6 CYB5R3 NM_000398.6(CYB5R3): c.446T> C (p.Leu149Pro) single nucleotide variant Pathogenic rs121965008 GRCh37 Chromosome 22, 43024175: 43024175
7 CYB5R3 NM_000398.6(CYB5R3): c.446T> C (p.Leu149Pro) single nucleotide variant Pathogenic rs121965008 GRCh38 Chromosome 22, 42628169: 42628169
8 CYB5R3 NM_000398.6(CYB5R3): c.316G> A (p.Val106Met) single nucleotide variant Pathogenic rs121965009 GRCh37 Chromosome 22, 43026905: 43026905
9 CYB5R3 NM_000398.6(CYB5R3): c.316G> A (p.Val106Met) single nucleotide variant Pathogenic rs121965009 GRCh38 Chromosome 22, 42630899: 42630899
10 CYB5R3 NM_000398.6(CYB5R3): c.734-1G> T single nucleotide variant Pathogenic rs794728011 GRCh37 Chromosome 22, 43015952: 43015952
11 CYB5R3 NM_000398.6(CYB5R3): c.734-1G> T single nucleotide variant Pathogenic rs794728011 GRCh38 Chromosome 22, 42619946: 42619946
12 CYB5R3 NM_000398.6(CYB5R3): c.463+8G> C single nucleotide variant Pathogenic rs200872504 GRCh37 Chromosome 22, 43024150: 43024150
13 CYB5R3 NM_000398.6(CYB5R3): c.463+8G> C single nucleotide variant Pathogenic rs200872504 GRCh38 Chromosome 22, 42628144: 42628144
14 CYB5R3 NM_000398.6(CYB5R3): c.655C> T (p.Arg219Ter) single nucleotide variant Pathogenic rs121965010 GRCh37 Chromosome 22, 43019873: 43019873
15 CYB5R3 NM_000398.6(CYB5R3): c.610T> C (p.Cys204Arg) single nucleotide variant Pathogenic rs121965011 GRCh37 Chromosome 22, 43023333: 43023333
16 CYB5R3 NM_000398.6(CYB5R3): c.610T> C (p.Cys204Arg) single nucleotide variant Pathogenic rs121965011 GRCh38 Chromosome 22, 42627327: 42627327
17 CYB5R3 NM_000398.6(CYB5R3): c.817_819delATG (p.Met273del) deletion Pathogenic rs794728012 GRCh38 Chromosome 22, 42619860: 42619862
18 CYB5R3 NM_000398.6(CYB5R3): c.817_819delATG (p.Met273del) deletion Pathogenic rs794728012 GRCh37 Chromosome 22, 43015866: 43015868
19 CYB5R3 NM_000398.6(CYB5R3): c.895_897delTTC (p.Phe299del) deletion Pathogenic rs121965012 GRCh37 Chromosome 22, 43015788: 43015790
20 CYB5R3 NM_000398.6(CYB5R3): c.895_897delTTC (p.Phe299del) deletion Pathogenic rs121965012 GRCh38 Chromosome 22, 42619782: 42619784
21 CYB5R3 NM_000398.6(CYB5R3): c.464_547del single nucleotide variant Pathogenic rs794728013 GRCh38 Chromosome 22, 42627690: 42627690
22 CYB5R3 NM_000398.6(CYB5R3): c.464_547del single nucleotide variant Pathogenic rs794728013 GRCh37 Chromosome 22, 43023696: 43023696
23 CYB5R3 NM_000398.6(CYB5R3): c.218T> C (p.Leu73Pro) single nucleotide variant Pathogenic rs121965013 GRCh37 Chromosome 22, 43027392: 43027392
24 CYB5R3 NM_000398.6(CYB5R3): c.218T> C (p.Leu73Pro) single nucleotide variant Pathogenic rs121965013 GRCh38 Chromosome 22, 42631386: 42631386
25 CYB5R3 NM_000398.6(CYB5R3): c.229C> T (p.Gln77Ter) single nucleotide variant Pathogenic rs121965014 GRCh37 Chromosome 22, 43026992: 43026992
26 CYB5R3 NM_000398.6(CYB5R3): c.229C> T (p.Gln77Ter) single nucleotide variant Pathogenic rs121965014 GRCh38 Chromosome 22, 42630986: 42630986
27 CYB5R3 NM_000398.6(CYB5R3): c.478C> T (p.Arg160Ter) single nucleotide variant Pathogenic rs61732609 GRCh37 Chromosome 22, 43023680: 43023680
28 CYB5R3 NM_000398.6(CYB5R3): c.478C> T (p.Arg160Ter) single nucleotide variant Pathogenic rs61732609 GRCh38 Chromosome 22, 42627674: 42627674
29 CYB5R3 NM_000398.6(CYB5R3): c.611G> A (p.Cys204Tyr) single nucleotide variant Pathogenic rs121965015 GRCh37 Chromosome 22, 43023332: 43023332
30 CYB5R3 NM_000398.6(CYB5R3): c.611G> A (p.Cys204Tyr) single nucleotide variant Pathogenic rs121965015 GRCh38 Chromosome 22, 42627326: 42627326
31 CYB5R3 NM_000398.6(CYB5R3): c.875G> A (p.Gly292Asp) single nucleotide variant Pathogenic rs121965016 GRCh37 Chromosome 22, 43015810: 43015810
32 CYB5R3 NM_000398.6(CYB5R3): c.875G> A (p.Gly292Asp) single nucleotide variant Pathogenic rs121965016 GRCh38 Chromosome 22, 42619804: 42619804
33 CYB5R3 NM_000398.6(CYB5R3): c.766_768delGAG (p.Glu256del) deletion Pathogenic rs121965017 GRCh37 Chromosome 22, 43015917: 43015919
34 CYB5R3 NM_000398.6(CYB5R3): c.766_768delGAG (p.Glu256del) deletion Pathogenic rs121965017 GRCh38 Chromosome 22, 42619911: 42619913
35 CYB5R3 NM_000398.6(CYB5R3): c.719A> G (p.Asp240Gly) single nucleotide variant Pathogenic rs121965018 GRCh37 Chromosome 22, 43019809: 43019809
36 CYB5R3 NM_000398.6(CYB5R3): c.719A> G (p.Asp240Gly) single nucleotide variant Pathogenic rs121965018 GRCh38 Chromosome 22, 42623803: 42623803

Expression for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

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Pathways for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

GO Terms for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

Sources for Methemoglobinemia Due to Deficiency of Methemoglobin Reductase

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