MCID: MTH007
MIFTS: 46

Methemoglobinemia

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Methemoglobinemia

MalaCards integrated aliases for Methemoglobinemia:

Name: Methemoglobinemia 12 74 36 54 6 44 15 39 71

Classifications:



External Ids:

Disease Ontology 12 DOID:10783
KEGG 36 H00235
ICD9CM 34 289.7
MeSH 44 D008708
NCIt 50 C34817
SNOMED-CT 67 191386007
ICD10 32 D74
UMLS 71 C0025637

Summaries for Methemoglobinemia

KEGG : 36 Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase deficiency.

MalaCards based summary : Methemoglobinemia is related to methemoglobinemia, beta-globin type and congenital methemoglobinemia, and has symptoms including cyanosis An important gene associated with Methemoglobinemia is NT5M (5',3'-Nucleotidase, Mitochondrial), and among its related pathways/superpathways are Amino sugar and nucleotide sugar metabolism and Metabolism. The drugs Methylene blue and Levoleucovorin have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and kidney, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and Decreased shRNA abundance (Z-score < -2)

Wikipedia : 74 Methemoglobinemia is a condition of elevated methemoglobin in the blood. Symptoms may include headache,... more...

Related Diseases for Methemoglobinemia

Diseases in the Methemoglobinemia family:

Methemoglobinemia, Beta Type Methemoglobinemia, Alpha Type
Congenital Methemoglobinemia Acquired Methemoglobinemia

Diseases related to Methemoglobinemia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 265)
# Related Disease Score Top Affiliating Genes
1 methemoglobinemia, beta-globin type 32.7 LOC107133510 LOC106099062 HBB
2 congenital methemoglobinemia 32.4 SOD1 HBG2 G6PD CYB5R3 CYB5A
3 acquired methemoglobinemia 32.4 HBG2 G6PD CYB5R3
4 methemoglobinemia, beta type 32.2 LOC107133510 LOC106099062 HBB
5 glucosephosphate dehydrogenase deficiency 30.3 HP HBG2 HBB GSR G6PD
6 hemolytic anemia 30.3 LOC106099062 HP HBG2 HBB GSR G6PD
7 hemoglobin e disease 30.0 LOC107133510 LOC106099062 HBB
8 bilirubin metabolic disorder 29.9 HP HBG2 G6PD CYP3A4
9 heinz body anemias 29.9 LOC106099062 HP HBB CYB5R3
10 anemia, nonspherocytic hemolytic, due to g6pd deficiency 29.7 HP G6PD
11 sickle cell anemia 29.6 LOC106099062 HBG2 HBB G6PD
12 beta-thalassemia 29.5 LOC106099062 HBG2 HBB GSR G6PD
13 deficiency anemia 29.4 SOD1 NAT2 LOC106099062 HP HBG2 HBB
14 alpha-thalassemia 29.1 LOC107133510 LOC106099062 HP HBG2 HBB G6PD
15 malaria 29.0 SOD1 LOC106099062 HP HBB GSR G6PD
16 hemoglobinopathy 27.9 LOC107133510 LOC106099062 HP HBG2 HBB G6PD
17 methemoglobinemia due to deficiency of methemoglobin reductase 11.8
18 methemoglobinemia and ambiguous genitalia 11.6
19 methemoglobinemia, alpha type 11.3
20 cyanosis, transient neonatal 10.9
21 hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome 10.3 HBG2 HBB
22 methemoglobin reductase deficiency 10.3
23 hemoglobin e-beta-thalassemia syndrome 10.3 LOC106099062 HBB
24 sickle cell disease and related diseases 10.3 LOC106099062 HBB
25 diarrhea 10.3
26 respiratory failure 10.3
27 sulfhemoglobinemia 10.3
28 kidney disease 10.3
29 hemoglobin d disease 10.2 LOC107133510 HBB
30 leprosy 3 10.2
31 hansen's disease 10.2
32 hemoglobin c disease 10.2 LOC106099062 HBB
33 ocular motor apraxia 10.2
34 metabolic acidosis 10.2
35 alzheimer disease 13 10.2 CYP2E1 CYB5A
36 acute kidney failure 10.2
37 hemoglobin zurich 10.2 LOC107133510 LOC106099062 HBB
38 beta-thalassemia intermedia 10.2 LOC107133510 LOC106099062 HBB
39 hereditary persistence of fetal hemoglobin-sickle cell disease syndrome 10.2 LOC106099062 HBG2 HBB
40 beta-thalassemia, dominant inclusion body type 10.2 LOC107133510 LOC106099062 HBB
41 blackwater fever 10.2 HP G6PD
42 beta-thalassemia major 10.2 LOC107133510 LOC106099062 HBB
43 hemoglobin h disease 10.2 HBG2 HBB G6PD
44 lymphosarcoma 10.1 GSR G6PD
45 splenic sequestration 10.1 HP HBB
46 autosomal recessive disease 10.1
47 pneumonia 10.1
48 pulmonary embolism 10.1
49 splenic infarction 10.1 HP HBB
50 pneumocystosis 10.1

Graphical network of the top 20 diseases related to Methemoglobinemia:



Diseases related to Methemoglobinemia

Symptoms & Phenotypes for Methemoglobinemia

UMLS symptoms related to Methemoglobinemia:


cyanosis

GenomeRNAi Phenotypes related to Methemoglobinemia according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-100 9.44 NT5M
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-128 9.44 SOD1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-135 9.44 SOD1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-161 9.44 NT5M
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-209 9.44 CYP3A4
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-212 9.44 CYP3A4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-41 9.44 SOD1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 9.44 SOD1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-57 9.44 CYP3A4 SOD1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-65 9.44 NT5M
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-70 9.44 NT5M
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-85 9.44 NT5M

Drugs & Therapeutics for Methemoglobinemia

Drugs for Methemoglobinemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 35)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methylene blue Approved, Investigational Phase 4 61-73-4
2
Levoleucovorin Approved, Investigational Phase 1 68538-85-2 149436
3
Dapsone Approved, Investigational Phase 1 80-08-0 2955
4
Folic acid Approved, Nutraceutical, Vet_approved Phase 1 59-30-3 6037
5 Folic Acid Antagonists Phase 1
6 Vitamin B Complex Phase 1
7 Anti-Infective Agents Phase 1
8 Antiparasitic Agents Phase 1
9 Antiprotozoal Agents Phase 1
10 Anti-Bacterial Agents Phase 1
11 Vitamin B9 Phase 1
12 Antimalarials Phase 1
13 Folate Phase 1
14 Pharmaceutical Solutions Phase 1
15
Racepinephrine Approved 329-65-7 838
16
Lidocaine Approved, Vet_approved 137-58-6 3676
17
Prilocaine Approved 721-50-6 4906
18
Epinephrine Approved, Vet_approved 51-43-4 5816
19 Anesthetics
20 Adrenergic alpha-Agonists
21 Respiratory System Agents
22 Neurotransmitter Agents
23 Anti-Asthmatic Agents
24 Anti-Arrhythmia Agents
25 Sodium Channel Blockers
26 Adrenergic beta-Agonists
27 Epinephryl borate
28 Mydriatics
29 Anesthetics, Local
30 Diuretics, Potassium Sparing
31 Bronchodilator Agents
32 Adrenergic Agents
33 Sympathomimetics
34 Vasoconstrictor Agents
35 Adrenergic Agonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open Label Clinical Study to Evaluate the Safety and Efficacy of ProvayBlueTM (Methylene Blue) for the Treatment of Acquired Methemoglobinemia Recruiting NCT03395223 Phase 4 Methylene Blue
2 Pharmacokinetics and Distribution of Dapsone (DDS) in Leucocytes After Single-dose and Multiple-dose Administration in Healthy Subjects Genotyped for CYP2C9 and NAT2 and in Patients With Autoimmune Bullous Dermatoses Completed NCT02493283 Phase 1 Dapsone single dose;Dapsone multiple dose
3 A One-Period, Single-Dose, Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Injection USP Following a 1 mg/kg Intravenous Dose in Healthy Adult Volunteers Completed NCT02478281 Phase 1 Methylene Blue
4 Use of Methylene Blue in Acquired Methemoglobinemia: Prospective Observational Registry (metHb) Unknown status NCT03542760 Methylene Blue
5 Dapsone Induced Methemoglobinemia in Pediatric Hematologic Malignancy and Aplastic Anemia Completed NCT00993694 chemotherapy;dapsone
6 Accuracy of Detection of Methemoglobin With Pulse Oximetry Completed NCT03869840
7 Methemoglobinemia After Liposuction Under Tumescent Local Anesthesia - Timecourse and Diagnostics by Pulse Oximetry and Blood Gas Analysis. Completed NCT01766999
8 Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Prilocaine Versus Lidocaine Completed NCT01402869 4% prilocaine plain;2% Lidocaine with 1:100,000 epinephrine

Search NIH Clinical Center for Methemoglobinemia

Inferred drug relations via UMLS 71 / NDF-RT 51 :


Ascorbic Acid
Ascorbic Acid Powder
Methylene blue
Sodium Ascorbate

Cochrane evidence based reviews: methemoglobinemia

Genetic Tests for Methemoglobinemia

Anatomical Context for Methemoglobinemia

MalaCards organs/tissues related to Methemoglobinemia:

40
Skin, Brain, Kidney, Thyroid, Whole Blood, Tongue, Spleen

Publications for Methemoglobinemia

Articles related to Methemoglobinemia:

(show top 50) (show all 2402)
# Title Authors PMID Year
1
Methemoglobinemia presenting in a circumcised baby following application of prilocaine: a case report. 54 61
20181170 2010
2
[Acquired methemoglobinemia--case report]. 61 54
20306428 2010
3
A novel mutation in type II methemoglobinemia. 54 61
19471045 2010
4
Intraoperative diagnosis of unsuspected methemoglobinemia due to low pulse oximetry values. 61 54
19617227 2009
5
A novel L218P mutation in NADH-cytochrome b5 reductase associated with type I recessive congenital methemoglobinemia. 54 61
19579085 2009
6
A rare cause of mental motor retardation: recessive congenital methemoglobinemia type II. 61 54
19480335 2009
7
Methemoglobinemia related to local anesthetics: a summary of 242 episodes. 61 54
19224791 2009
8
Methemoglobinemia due to application of prilocaine during circumcision and the effect of ascorbic acid. 54 61
19013416 2008
9
Topical benzocaine-induced methemoglobinemia in the pediatric population. 61 54
18971079 2008
10
Exchange transfusion as treatment for rasburicase induced methemoglobinemia in a glucose-6-phosphate dehydrogenase deficient patient. 54 61
18561168 2008
11
[Establishment of a cellular model with human NADH-cytochrome b5 reductase deficiency via RNA interference]. 61 54
18683136 2008
12
A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. 61 54
17851637 2008
13
Severe methemoglobinemia and syncope in a patient with glucose-6-phosphate dehydrogenase deficiency. 54 61
17939637 2007
14
[Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine]. 61 54
17992408 2007
15
Rediscovery of the susceptibility of G6PD deficient persons to methemoglobinemia from oxidant drugs, and to hemolysis from methylene blue. 61 54
16917918 2007
16
The role of methemoglobinemia in early and late complicated pregnancy. 61 54
17112681 2007
17
Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature. 54 61
16585290 2006
18
Spotlight on rasburicase in anticancer therapy-induced hyperuricemia. 54 61
16724869 2006
19
Complications related to dapsone use for Pneumocystis jirovecii pneumonia prophylaxis in solid organ transplant recipients. 61 54
16212642 2005
20
Hemolysis and methemoglobinemia secondary to rasburicase administration. 54 61
16204390 2005
21
A case with quadriparetic cerebral palsy and cyanosis: congenital methemoglobinemia. 54 61
16087059 2005
22
Methemoglobinemia induced by topical vaginal sulfanilamide cream in a patient with cervical cancer: a case report. 54 61
15907987 2005
23
Prophylactic methylene blue in a patient with congenital methemoglobinemia. 54 61
15753496 2005
24
Methemoglobinemia in children with acute lymphoblastic leukemia (ALL) receiving dapsone for pneumocystis carinii pneumonia (PCP) prophylaxis: a correlation with cytochrome b5 reductase (Cb5R) enzyme levels. 54 61
15390276 2005
25
Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. 54 61
15587250 2004
26
Prilocaine plasma levels and methemoglobinemia in patients undergoing tumescent liposuction involving less than 2,000 ml. 61 54
15870963 2004
27
[Methemoglobinemia due to prilocaine after plexus anesthesia. Reduction by prophylactic administration of ascorbic acid?]. 54 61
14992088 2003
28
The structure of the S127P mutant of cytochrome b5 reductase that causes methemoglobinemia shows the AMP moiety of the flavin occupying the substrate binding site. 61 54
14609324 2003
29
Anesthetic management of a patient with methemoglobinemia. 54 61
12911193 2003
30
Severe methemoglobinemia after transesophageal echocardiography. 54 61
12756430 2003
31
Methemoglobinemia following unintentional ingestion of sodium nitrite--New York, 2002. 61 54
12186221 2002
32
Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. 54 61
11824767 2002
33
Metoclopramide-induced methemoglobinemia in a patient with co-existing deficiency of glucose-6-phosphate dehydrogenase and NADH-cytochrome b5 reductase: failure of methylene blue treatment. 54 61
11418378 2001
34
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. 54 61
11295830 2001
35
A Thai boy with hereditary enzymopenic methemoglobinemia type II. 61 54
11215870 2000
36
[Acute dapsone exposure and methemoglobinemia in children: treatment with multiple doses of activated charcoal with or without the administration of methylene blue] 54 61
14647658 2000
37
Metoclopramide-induced methemoglobinemia in an adult. 54 61
10870338 2000
38
A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. 54 61
10807796 2000
39
Combined effects of inhaled nitric oxide (iNO) and oxidant agents on the production of methemoglobinemia in newborn piglets. 61 54
10809284 2000
40
A case of methemoglobinemia type II due to NADH-cytochrome b5 reductase deficiency: determination of the molecular basis. 61 54
10874300 2000
41
[A novel point mutation in NADH-cytochrome b5 reductase gene]. 54 61
11721397 1999
42
Hb Chile [beta28(B10)Leu-->Met]: an unstable hemoglobin associated with chronic methemoglobinemia and sulfonamide or methylene blue-induced hemolytic anemia. 61 54
10335980 1999
43
Methemoglobinemia induced by methylene blue pertubation during laparoscopy. 54 61
9605379 1998
44
Antibody-based spot test for NADH-cytochrome b5 reductase activity for the laboratory diagnosis of congenital methemoglobinemia. 54 61
9620466 1998
45
A systematic review of lidocaine-prilocaine cream (EMLA) in the treatment of acute pain in neonates. 54 61
9445511 1998
46
Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn. 61 54
9347001 1997
47
Methodologic problems encountered with cooximetry in methemoglobinemia. 61 54
9298047 1997
48
Methemoglobinemia caused by topical benzocaine. 54 61
9324196 1997
49
Methemoglobinemia induced by an over-the-counter medication. 61 54
8913407 1996
50
Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals. 61 54
8757424 1996

Variations for Methemoglobinemia

ClinVar genetic disease variations for Methemoglobinemia:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NT5M GRCh37/hg19 17p11.2(chr17:16936603-18184130) copy number loss Pathogenic 523258 17:16936603-18184130

Expression for Methemoglobinemia

Search GEO for disease gene expression data for Methemoglobinemia.

Pathways for Methemoglobinemia

Pathways related to Methemoglobinemia according to KEGG:

36
# Name Kegg Source Accession
1 Amino sugar and nucleotide sugar metabolism hsa00520

Pathways related to Methemoglobinemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.79 NT5M NAT2 HBB GSR G6PD CYP3A4
2
Show member pathways
12.77 NAT2 GSR CYP3A4 CYP2E1 CYB5R3 CYB5R2
3 11.81 GSR G6PD BLVRB
4
Show member pathways
11.44 CYB5RL CYB5R3 CYB5R2 CYB5R1
5
Show member pathways
11.02 NAT2 CYP3A4 CYP2E1
6 10.84 CYP3A4 CYP2E1
7
Show member pathways
10.8 HBB CYB5RL CYB5R2 CYB5R1
8 10.73 CYP3A4 CYP2E1
9 10.66 GSR G6PD
10 9.53 G6PD CYB5R3 CYB5A BLVRB

GO Terms for Methemoglobinemia

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

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 9.7 CYP3A4 CYP2E1 CYB5RL CYB5R3 CYB5R2 CYB5R1
2 blood microparticle GO:0072562 9.54 HP HBG2 HBB
3 organelle membrane GO:0031090 9.5 CYP3A4 CYP2E1 CYB5A
4 endocytic vesicle lumen GO:0071682 9.26 HP HBB
5 hemoglobin complex GO:0005833 9.13 HBG2 HBB CYB5R3
6 haptoglobin-hemoglobin complex GO:0031838 8.8 HP HBG2 HBB

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

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.91 G6PD CYP3A4 CYP2E1 CYB5R3 CYB5R2 CYB5R1
2 response to ethanol GO:0045471 9.74 SOD1 G6PD CYP2E1
3 cellular response to oxidative stress GO:0034599 9.72 SOD1 GSR G6PD
4 response to hydrogen peroxide GO:0042542 9.67 SOD1 HP HBB
5 xenobiotic metabolic process GO:0006805 9.67 NAT2 CYP3A4 CYP2E1 CYB5R3
6 glutathione metabolic process GO:0006749 9.63 SOD1 GSR G6PD
7 cellular oxidant detoxification GO:0098869 9.62 HP HBG2 HBB GSR
8 hydrogen peroxide catabolic process GO:0042744 9.6 HBG2 HBB
9 drug metabolic process GO:0017144 9.59 CYP3A4 CYP2E1
10 long-chain fatty acid biosynthetic process GO:0042759 9.58 CYP3A4 CYP2E1
11 exogenous drug catabolic process GO:0042738 9.58 CYP3A4 CYP2E1
12 sterol biosynthetic process GO:0016126 9.58 CYB5R3 CYB5R2 CYB5R1
13 oxygen transport GO:0015671 9.56 HBG2 HBB
14 steroid biosynthetic process GO:0006694 9.56 CYP3A4 CYB5R3 CYB5R2 CYB5R1
15 steroid metabolic process GO:0008202 9.55 CYP3A4 CYP2E1 CYB5R3 CYB5R2 CYB5R1
16 L-ascorbic acid metabolic process GO:0019852 9.54 CYB5R3 CYB5A
17 heterocycle metabolic process GO:0046483 9.52 CYP3A4 CYP2E1
18 lipid hydroxylation GO:0002933 9.51 CYP3A4 CYP2E1
19 monoterpenoid metabolic process GO:0016098 9.48 CYP3A4 CYP2E1
20 oxidation-reduction process GO:0055114 9.36 SOD1 GSR G6PD CYP3A4 CYP2E1 CYB5RL
21 bicarbonate transport GO:0015701 9.26 HBB CYB5RL CYB5R2 CYB5R1

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

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 enzyme binding GO:0019899 9.8 SOD1 CYP3A4 CYP2E1 CYB5A
2 heme binding GO:0020037 9.65 HBG2 HBB CYP3A4 CYP2E1 CYB5A
3 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0016712 9.54 CYP3A4 CYP2E1
4 antioxidant activity GO:0016209 9.52 SOD1 HP
5 aromatase activity GO:0070330 9.51 CYP3A4 CYP2E1
6 FAD binding GO:0071949 9.5 CYB5R3 CYB5R2 CYB5R1
7 oxygen carrier activity GO:0005344 9.48 HBG2 HBB
8 organic acid binding GO:0043177 9.46 HBG2 HBB
9 oxygen binding GO:0019825 9.46 HBG2 HBB CYP3A4 CYP2E1
10 haptoglobin binding GO:0031720 9.43 HBG2 HBB
11 hemoglobin alpha binding GO:0031721 9.4 HBG2 HBB
12 hemoglobin binding GO:0030492 9.37 HP HBB
13 oxidoreductase activity GO:0016491 9.32 SOD1 GSR G6PD CYP3A4 CYP2E1 CYB5RL
14 cytochrome-b5 reductase activity, acting on NAD(P)H GO:0004128 9.26 CYB5RL CYB5R3 CYB5R2 CYB5R1

Sources for Methemoglobinemia

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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