Methemoglobinemia
| Methemoglobinemia | |
| ICD-10 | D74 |
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| ICD-9 | 289.7 |
| DiseasesDB | 8100 |
| MeSH | D008708 |
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Methemoglobinemia Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Methemoglobinemia On the Web |
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American Roentgen Ray Society Images of Methemoglobinemia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Synonyms and keywords: Methaemoglobinaemia; methemoglobinaemia; methemoglobinuria
Overview
Historical Perspective
Classification
Classification
Pathophysiology
Causes
Causes
Differentiating Methemoglobinemia from other Diseases
Differential Diagnosis
Epidemiology and Demographics
Epidemiology
In the United States congenital methemoglobinemia is rare. Deficiency of cytochrome b5 reductase endemic only in some Native American tribes like Navajo and Athabaskan Alaskans, and the Yakutsk people in Siberia.
The acquired methemoglobinemia is the most common form, and most cases are related to topical or local anesthetic use during medical procedures.
Demographics
Infants, particularly those younger than 4 months are most susceptible to methemoglobinemia. This is due to the fact that the NADH methemoglobin reductase activity and concentration (the main protective enzyme against oxidative stress) is not fully mature in infants. Both cytochrome b5 reductase deficiency and pyruvate kinase deficiency are autosomal recessive diseases and the Hb M has autosomal dominant pattern of inheritance. On the other hand G6PD deficiency is X-linked, therefore the risk of acquired methemoglobinemia is greater in males. The highest prevalence of G6PD deficiency is observed in the malaria-endemic regions: Sub-Saharan Afria, West Asia and Arabian Peninsula, as well as in people of Mediterranean descent. As a result these populations are at higher risk for acquired methemoglobinemia.
Risk Factors
Risk Factors
Congenital (Hereditary) Methemoglobinemia
There are three main congenital conditions that lead to methemoglobinemia:
1. Cytochrome b5 reductase deficiency and pyruvate kinase deficiency
2. G6PD deficiency
3. Presence of abnormal hemoglobin (Hb M)
Both cytochrome b5 reductase deficiency and pyruvate kinase deficiency can lead to NADH deficiency which in turn will lead to decreased ability to remove MetHb from the blood. Cytochrome b5 reductase deficiency is an autosomal recessive disorder with at least 2 forms that we know of.
The most common form, is the Ib5R deficiency, where cyt b5 reductase is absent only in RBCs, and the levels of MetHb are around 10% to 35%.
The second type, which is much less common, is the IIb5R, where MetHb varies between 10% and 15% and the cyt b5 reductase is absent in all cells. This form is associated with mental retardation, microcephaly, and other neurologic problems. The lifespan of the affected individuals is greatly affected and patients usually die very young.
Congenital deficiency in G6PD can lead to decreased levels of NADPH and thus compromising the function of the diaphorase II enzyme system.
Abnormal hemoglobins like Hb M, including Hb Ms, Hb MIwate, Hb MBoston, Hb MHyde Park, and Hb MSaskatoon, an autosomal dominant condition, can also lead to methemoglobinemia. In case of amino acid substitution in the alpha-chain of hemoglobin, we observe cyanosis at birth, and infants with beta chain amino acid substitution will present with cyanosis later around 4-6 months of age.
Acquired methemoglobinemia
The acquired methemoglobinemia is significantly more common than the congenital one. It is associated with exposure to or ingestion of oxidant drugs, toxins or chemicals, that cause acute increment in methemoglobin levels, by overwhelming the normal physiologic protective enzyme mechanisms. The most common agents are anesthetics like benzocaine, lidocaine, prilocaine, used locally or topically, antibiotics like dapsone (used for the treatment of Brown Recluse spider bites, Leprosy, PCP prophylaxis, ecc) trimethoprim, sulfonamides, nitrates (amynitrate), nitroglycerin (NG), aniline dyes, metoclopramide, chlorates and bromates.
Drug Induced
• Anesthetics like benzocaine, lidocaine, prilocaine
• Methylene blue
• Nitric oxide
• Amilnitrate
• Nitroglycerin
• Antimalarial drugs like Primaquine phosphate (in nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficient individuals)
• Rasburicase
• Sulfasalazine
• Dapsone
• Trimethoprim
• Sulfonamides
• Aniline dyes
• Metoclopramide
• Chlorates and Bromates and others
Contaminated well water (in premature infants and infants younger than 4 months)
Solid foods (not well cooked vegetables high in nitrates in premature infants and infants younger than 4 months)
Screening
Currently we have a screening test for G6PD deficiency. It is called methemoglobin reduction test (MRT), it is not expensive and it uses cord blood of neonates to check for the enzyme deficiency. Even though it has low sensitivity around 65%, it does have acceptable specificity around[1] 90%.
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case Studies
- ↑ PMID: 11529386