MCID: HRD146
MIFTS: 29

Hereditary Methemoglobinemia

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Hereditary Methemoglobinemia

MalaCards integrated aliases for Hereditary Methemoglobinemia:

Name: Hereditary Methemoglobinemia 53 59 6
Congenital Methemoglobinemia 53 59 72
Autosomal Recessive Methemoglobinemia 53 59
Methemoglobinemia Hereditary 55
Hemoglobin M Disease 72

Characteristics:

Orphanet epidemiological data:

59
hereditary methemoglobinemia
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

ICD10 via Orphanet 34 D74.0
UMLS via Orphanet 73 C0272087
Orphanet 59 ORPHA621
UMLS 72 C0272087 C3665425

Summaries for Hereditary Methemoglobinemia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 621DefinitionA rare red cell disorder classified principally into two clinical phenotypes: autosomal recessive congenital (or hereditary) methemoglobinemia types I and II (RCM/RHM type 1; RCM/RHM type 2).Clinical descriptionIn RCM type 1, cyanosis from birth is the only symptom. It is well-tolerated and is associated with mild complaints of headaches, fatigue and shortness of breath upon exertion. RCM type 2 is much more severe; the cyanosis is accompanied by neurological dysfunction (with intellectual deficit, microcephaly, growth retardation, opisthotonus, strabismus and hypertonia), which usually becomes evident during the first four months of life. Two additional forms of RCM have also been reported. RCM type 3 was the term used to define a phenotype with cyanosis but without neurological abnormalities in which Cb5R deficiency was identified in leucocytes and platelets as well as erythrocytes. This distinction has been largely ignored in subsequent reports of other CYB5R3 variants, so the term RCM type 3 is rarely used. RCM type 4 is a very rare disease associated with chronic cyanosis caused by mutations in the CYB5A gene (18q23) encoding cytochrome b5. In addition, there have been two reports of NADPH reductase deficiency, but in one case (identified though an inability to metabolize methylene blue) methemoglobinemia was not present suggesting that this pathway has limited physiological importance. It is also possible that mutations of the substrate of NADPH reductase, which remains to be identified, could have a minor effect on the reduction of methemoglobin.EtiologyRCM type 1 is caused by mutations of the CYB5R3 gene (22q13.31-qter) encoding the NADH-cytochrome b5 reductase (Cb5R) and Cb5R deficiency is limited to the erythrocytes. RCM type 2 is caused by global loss of Cb5R function. Over 40 different CYB5R3 mutations have been identified so far, some of which have been identified in both types. RCM type 1 is generally associated with missense mutations, whereas RCM type 2 is more commonly associated with truncating mutations, splicing errors or mutations that lead to disruption of the active site.Management and treatmentTreatment of methemoglobinemia revolves around administration of methylene blue and/or ascorbic acid. Although ascorbic acid alone is sufficient to alleviate the cyanosis in milder cases, the reaction rate is slower than that of the combined treatment. However, these treatments have no effect on the neurological dysfunction in RCM type 2.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hereditary Methemoglobinemia, also known as congenital methemoglobinemia, is related to methemoglobinemia and acquired methemoglobinemia. An important gene associated with Hereditary Methemoglobinemia is CYB5R3 (Cytochrome B5 Reductase 3), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Methylene Blue Pathway, Pharmacodynamics. Affiliated tissues include kidney, brain and liver.

Related Diseases for Hereditary Methemoglobinemia

Graphical network of the top 20 diseases related to Hereditary Methemoglobinemia:



Diseases related to Hereditary Methemoglobinemia

Symptoms & Phenotypes for Hereditary Methemoglobinemia

Drugs & Therapeutics for Hereditary Methemoglobinemia

Search Clinical Trials , NIH Clinical Center for Hereditary Methemoglobinemia

Genetic Tests for Hereditary Methemoglobinemia

Anatomical Context for Hereditary Methemoglobinemia

MalaCards organs/tissues related to Hereditary Methemoglobinemia:

41
Kidney, Brain, Liver, Heart, Spleen, Placenta, Cerebellum

Publications for Hereditary Methemoglobinemia

Articles related to Hereditary Methemoglobinemia:

(show top 50) (show all 241)
# Title Authors PMID Year
1
Congenital methemoglobinemia with a deficiency of cytochrome b5. 38 71
3951505 1986
2
A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency. 71
22170710 2012
3
Isolated 17,20-lyase deficiency due to the cytochrome b5 mutation W27X. 71
20080843 2010
4
The human cytochrome b5 gene and two of its pseudogenes are located on chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively. 71
8262522 1993
5
Recessive hereditary methemoglobinemia: two novel mutations in the NADH-cytochrome b5 reductase gene. 9 38
18343696 2008
6
A novel G143D mutation in the NADH-cytochrome b5 reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia. 9 38
17964195 2008
7
NADH cytochrome b5 reductase and cytochrome b5 catalyze the microsomal reduction of xenobiotic hydroxylamines and amidoximes in humans. 9 38
15302896 2004
8
[A search for mutations in the DIA1 gene in case of hereditary methemoglobinemia type I in the iakut population]. 9 38
12884529 2003
9
Molecular basis of recessive congenital methemoglobinemia, types I and II: Exon skipping and three novel missense mutations in the NADH-cytochrome b5 reductase (diaphorase 1) gene. 9 38
11295830 2001
10
A compound heterozygote in the NADH-cytochrome b5 reductase gene from a Chinese patient with hereditary methemoglobinemia type I. 9 38
10979206 2000
11
[Hereditary methemoglobinemias]. 9 38
10855391 2000
12
[Leu 72 Pro mutation in the NADH-cytochrome b5 reductase gene found in a Chinese hereditary methemoglobinemia patient]. 9 38
11243135 1998
13
Determination of concentration of cytosolic NADH-cytochrome b5 reductase in erythrocytes from normal Chinese adults, neonates and patients with hereditary methemoglobinemia by double-antibody sandwich ELISA. 9 38
9691146 1998
14
[Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia]. 9 38
15622768 1997
15
Two novel mutations in the reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase gene of a patient with generalized type, hereditary methemoglobinemia. 9 38
8874222 1996
16
Establishment of monoclonal antibodies against human erythrocyte NADH-cytochrome b5 reductase. 9 38
8880217 1996
17
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. 9 38
7668255 1995
18
[Congenital methemoglobinemia]. 9 38
8657061 1995
19
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. 9 38
8119939 1994
20
Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). 9 38
1400360 1992
21
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. 9 38
1707593 1991
22
Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type. 9 38
2107882 1990
23
[Molecular analysis of the structure of the mutant NADH-cytochrome b5 reductase gene causing methemoglobinemia]. 9 38
2323714 1990
24
Hereditary methemoglobinemia caused by Hb M-Hyde Park (Hb M-Akita) (HBB:c.277C > T; p.His93Tyr). 38
31267164 2019
25
Exon sequencing of the alpha-2-globin gene for the differential diagnosis of central cyanosis in newborns: a case report. 38
31269924 2019
26
Hereditary methemoglobinemia in a cyanotic cat presented for ovariohysterectomy. 38
31080263 2019
27
Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene. 38
30614390 2019
28
Genetic cause for congenital methemoglobinemia in an Australian Pomeranian dog. 38
30767280 2019
29
Congenital Methemoglobinemia Identified by Pulse Oximetry Screening. 38
30733239 2019
30
'Acute leukemia in congenital methehemoglobinemia - an enigma to explore'. 38
30788079 2019
31
Novel mutation (R192C) in CYB5R3 gene causing NADH-cytochrome b5 reductase deficiency in eight Indian patients associated with autosomal recessive congenital methemoglobinemia type-I. 38
29482478 2018
32
[Cyanosis in 14-year-old patient. Methemoglobinemia: case report]. 38
29756717 2018
33
Failure of Pulse Oximetry and Cooximetry as Monitors in a Patient With Hemoglobin MIwate: A Case Report. 38
29293483 2018
34
The Acute Treatment of Methemoglobinemia in Pregnancy. 38
29627348 2018
35
A new mutation of congenital methemoglobinemia exacerbated after methylene blue treatment. 38
29657736 2018
36
Congenital methemoglobinemia misdiagnosed as polycythemia vera: Case report and review of literature. 38
29721250 2018
37
Congenital methemoglobinemia type II in a 5-year-old boy. 38
29375859 2018
38
Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH-Cytochrome B5 Reductase Gene. 38
29356095 2018
39
Congenital Methemoglobinemia: It is Time for National Level Registry System. 38
28991125 2017
40
Long-term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency. 38
28963729 2017
41
Anesthetic management of congenital methemoglobinemia in an emergency cesarean section. 38
29109650 2017
42
Patient with Persistent Low Oxygen Saturation for Emergency Cesarean Section. 38
28928588 2017
43
Methemoglobinemia: Living with Dormant Devil. 38
28428705 2017
44
A microplate reader-based method to quantify NADH-cytochrome b5 reductase activity for diagnosis of recessive congenital methaemoglobinemia. 38
27863456 2017
45
Enzymopenic Congenital Methemoglobinemia in Children of the Republic of Sakha (Yakutia). 38
27879543 2017
46
Congenital methemoglobinemia type 2 and cerebellar atrophy/hypoplasia. 38
26133947 2016
47
High expression of cytochrome b 5 reductase isoform 3/cytochrome b 5 system in the cerebellum and pyramidal neurons of adult rat brain. 38
25850901 2016
48
Congenital Methemoglobinemia Type II-Clinical Improvement with Short-Term Methylene Blue Treatment. 38
26574897 2016
49
Recessive congenital methemoglobinemia in immediate generations. 38
27922248 2016
50
A novel nine base deletion mutation in NADH-cytochrome b5 reductase gene in an Indian family with recessive congenital methemoglobinemia-type-II. 38
28649542 2015

Variations for Hereditary Methemoglobinemia

ClinVar genetic disease variations for Hereditary Methemoglobinemia:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 CYB5R3 NM_000398.7(CYB5R3): c.757G> A (p.Val253Met) single nucleotide variant Pathogenic rs144071404 22:43015928-43015928 22:42619922-42619922

Expression for Hereditary Methemoglobinemia

Search GEO for disease gene expression data for Hereditary Methemoglobinemia.

Pathways for Hereditary Methemoglobinemia

GO Terms for Hereditary Methemoglobinemia

Cellular components related to Hereditary Methemoglobinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial outer membrane GO:0005741 8.96 CYB5R3 CYB5A
2 hemoglobin complex GO:0005833 8.62 HBG2 CYB5R3

Biological processes related to Hereditary Methemoglobinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 L-ascorbic acid metabolic process GO:0019852 8.62 CYB5R3 CYB5A

Molecular functions related to Hereditary Methemoglobinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 8.62 HBG2 CYB5A

Sources for Hereditary Methemoglobinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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