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FACT SHEET: Glucose-6-Phosphate Dehydrogenase Deficiency (also known as “G6PD deficiency” and “erythrocyte glucose-6-phosphate dehydrogenase deficiency”; includes “favism”)

Date of Publication: October 14, 2020
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Note: For more detail on the general manifestations of anemia, and those of hemolytic anemia in particular, please refer to the Anemia Fact Sheet.

Is the initiation of non-invasive dental hygiene procedures* contra-indicated?

  • No.

Is medical consult advised? 

  • Yes, if G6PD deficiency is newly suspected.1
  • Yes, if a patient/client with known G6PD deficiency has been recently exposed to a trigger that could cause acute hemolytic anemia (AHA) or methemoglobinemia. 
  • Yes, if an episode of acute hemolytic anemia or methemoglobinemia is suspected. Acute hemolytic crisis (the severest form of AHA) is a medical emergency, which necessitates immediate referral and transfer to an appropriate facility for management.2 Severe methemoglobinemia3 is also a medical emergency.
  • Yes, if the patient/client has chronic hemolytic anemia or methemoglobinemia, in which case liaison with the patient/client’s hematologist (blood specialist) or experienced internist, paediatrician, or family physician is advisable regarding the severity and management of the patient/client’s disorder before undertaking dental hygiene treatment for the first time.

 

Is the initiation of invasive dental hygiene procedures contra-indicated?**

  • Yes. This metabolic condition entails blood disorders (hemolytic anemia4 and methemoglobinemia) that may affect appropriateness or safety, and scaling and root planing, including curetting surrounding tissue, are contraindicated until the patient/client is medically cleared (as per Ontario Regulation 510/07 pursuant to the Dental Hygiene Act, 1991). Another potential contraindication is hypersplenism, which can cause thrombocytopenia (i.e., low platelet count, and hence increased risk of bleeding) and/or neutropenia (i.e., low neutrophil white blood cell count, and hence compromised immunity and increased risk of infection).

Is medical consult advised? 

  • See above. 

Is medical clearance required? 

  • Yes, if G6PD deficiency and/or hemolytic anemia and/or methemoglobinemia have been diagnosed or are suspected. (Note: Most patients/clients with G6PD deficiency, in the absence of a trigger, are merely at elevated risk of hemolytic anemia or methemoglobinemia rather than actually having it or exhibiting clinically relevant signs/symptoms.)
  • Yes, if significant thrombocytopenia exists or is suspected. 
  • Yes, if significant neutropenia exists or is suspected. 

Is antibiotic prophylaxis required? 

  • No, in most cases.
  • Potentially, if significant neutropenia exists.5 

Is postponing treatment advised?

  • Yes, pending medical clearance (and potential preventive measures or treatment for hemolytic anemia or methemoglobinemia, as indicated). 
  • Yes, if patient/client has recently been exposed to a trigger for hemolytic anemia or methemoglobinemia, including certain drugs, infections (including uncontrolled oral infections), and metabolic conditions, as well as fava beans. 
  • Yes, if an episode of acute hemolytic anemia or methemoglobinemia is suspected.
  • Yes, if chronic hemolytic anemia or methemoglobinemia is suspected to be severe and the patient/client has attendant signs/symptoms. Patients/clients who are short of breath and in whom hemoglobin (Hb) levels are < 110 g/L [also expressed as 11.0 g/dL], have an abnormal heart rate, or have an oxygen saturation < 91% (as determined by pulse oximetry) are considered medically unstable, and routine dental/dental hygiene treatment should be deferred until health status improves.

Oral management implications

  • Of chief concern to oral healthcare professionals, certain medications (including some antibiotics and analgesics) can precipitate an acute hemolytic crisis (very rapid red blood cell breakdown) in some patients/clients with G6PD deficiency.6 These include sulfa drugs (e.g., sulfacetamide, sulfadiazine, sulfamethoxazole, sulfanilamide, sulfapyridine, and dapsone); certain other antibiotics (such as quinolones [e.g., ciprofloxacin, moxifloxacin, nalidixic acid, and norfloxacin], some anti-tuberculosis drugs [e.g., isoniazid and streptomycin], as well as nitrofurantoin, cotrimoxazole, and furazolidone)7; certain analgesics (including acetylsalicylic acid [i.e., ASA, particularly in high doses] and phenazopyridine [a urinary analgesic]); certain antimalarial drugs (e.g., chloroquine, pentaquine, primaquine, and quinine); certain anti-arrhythmic agents (e.g., quinidine); certain chemotherapy drugs (e.g., doxorubicin); certain antihelminthic8 agents (e.g., niridazole); certain chelating agents (e.g., dimercaprol, which is used to treat acute poisoning by arsenic, mercury, gold, and lead); rasburicase (used to lower uric acid levels, particularly in persons undergoing treatment for leukemia, lymphoma, and certain tumours); certain anti-diabetes agents (particularly the first-generation sulfonylurea chlorpropamide); methylene blue (used to treat methemoglobinemia, and also a component of some urinary tract products); toluidine blue (a dye which has been used in vivo to identify dysplasia and carcinoma of the oral cavity); and ascorbic acid (vitamin C). In addition, camphor (a wood oil commonly used in creams, lotions, and ointments) and henna compounds can be a trigger. The degree of susceptibility varies between persons, with persons with lower degrees of residual G6PD activity being at higher risk and having more limitations with respect to “probably safe” drugs.
  • Acetaminophen use within recommended therapeutic dosages is generally considered safe for most persons with G6PD deficiency (i.e., those with Class II deficiency or higher, without nonspherocytic hemolytic anemia).9 Similarly, many non-steroidal anti-inflammatory drugs within recommended dosages are probably safe for most persons with G6PD deficiency.10
  • Infection — including uncontrolled oral infection — is a trigger for acute hemolytic anemia in some patients/clients with G6PD deficiency.11 Dental infections should be avoided, and if they occur, be managed quickly and effectively. Periodontal disease should proactively managed.   
  • In persons living with G6PD-deficiency, methemoglobinemia can be caused by many of the same oxidative stressors that trigger acute hemolytic crisis.
  • Local anaesthetic agents (e.g., prilocaine, lidocaine, and articaine), topical benzocaine, and silver nitrate have been reported to induce methemoglobinemia in G6PD deficient persons. However, as with analgesics and antibiotics commonly used in the dental setting, there is considerable debate regarding which anaesthetic drugs should be generally or selectively avoided. While inhalation sedation is usually safe, general anaesthesia should generally be given in a hospital environment.

Oral manifestations

  • In the absence of hemolytic anemia, methemoglobinemia, and hypersplenism, G6PD deficiency typically exhibits no overt or distinctive facial or bucodental signs.
  • Jaundice12 (yellowing), pallor13, and/or cyanosis14 of oral mucous membranes and perioral skin may be present.
  • Gingival swelling and bleeding may occur, as may palatal petechiae and ecchymoses (i.e., discolouration from bruising).
  • Progressive spacing between teeth (especially anterior maxillary and mandibular) can occur if gingival swelling is chronic or chronically recurrent.
  • Blood may be chocolate brown in colour if there is methemoglobinemia.

Related signs and symptoms

  • G6PD deficiency is a genetic metabolic abnormality involving the glucose-6-phosphate dehydrogenase enzyme.15 A low enzyme level can impair the ability of red blood cells (RBCs) to manage oxidative stress, leading to hemolysis (cell destruction) and/or hemoglobin oxidation (methemoglobinemia). When the body cannot compensate for accelerated loss of RBCs, anemia occurs. However, in most affected persons, deficiency of G6PD in and of itself is insufficient to cause hemolysis or significant methemoglobinemia16 — a trigger is required.17
  • G6PD deficiency may occur by a new (sporadic) genetic mutation, or be inherited in an X-chromosome-linked manner.18 There is a range of variants, from near normal to severe deficiency to chronic hemolytic anemia even in the absence of triggers.)
  • G6PD deficiency is one of the most common enzyme deficiencies, affecting between 400 million and 500 million persons globally. Many authorities assert that it affects males more than females, although this is disputed by others. While individuals of all races and ethnic backgrounds are affected, persons of black African, Middle Eastern (particularly Kurdish and Sephardic Jewish), certain Mediterranean (e.g., Sardinian), certain Asian (e.g., southern Chinese and Southeast Asian), and central and southern Pacific island backgrounds have the highest prevalence rates. Although overall world-wide prevalence is high, the vast majority of persons remain clinically asymptomatic throughout their lives, and therefore overt disease is rare. The severe form of the disorder occurs most often in persons of Mediterranean or Asian background.
  • G6PD deficiency — in the absence of hemolytic anemia, methemoglobinemia, and hypersplenism — typically exhibits no overt or distinctive physical signs/symptoms.
  • Triggers that cause hemolytic anemia and/or methemoglobinemia in G6PD-deficient persons include certain drugs, certain infectious diseases, certain metabolic conditions (e.g., diabetic ketoacidosis), and eating fava beans (i.e., broad beans). In addition, naphthalene — found in mothballs — is a trigger. Some persons with G6PD deficiency should also avoid red wine, blueberries, all beans, soya products, and tonic water. In the absence of triggering factors19, most persons are asymptomatic, and many persons proceed throughout life without any knowledge or noticeable signs/symptoms of the disorder.
  • Clinical manifestations of G6PD deficiency, which involves intravascular hemolysis, include acute and chronic hemolytic anemia with methemoglobinemia, neonatal bilirubinemia, and neonatal jaundice.
  • Onset of signs/symptoms of acute hemolytic anemia is typically within 2 to 3 days after exposure to the trigger, and even less with fava beans.20
  • Signs/symptoms of G6PD deficiency related to anemia and hemolysis include: fatigue, pallor, jaundice (yellowing of eyes, skin, and mucous membranes), dyspnea (shortness of breath), headache, tachycardia (elevated resting heartrate), palpitations, dizziness, cold extremities, lumbar/substernal pain, a sudden rise in body temperature, dark (tea-coloured) urine, and splenomegaly (enlarged spleen). An episode of hemolytic anemia may be preceded by irritability and/or lethargy. While most episodes of G6PD deficiency related acute hemolytic anemia are self-limiting and resolve on their own21, AHA is potentially life-threatening in its acute hemolytic crisis form.
  • Gastrointestinal sign/symptoms may occur with hemolytic anemia, including nausea, diarrhea, and abdominal pain.
  • Acute kidney injury can result from severe hemolysis.
  • If a considerable proportion of hemolysis of red blood cells occurs in the spleen, hypersplenism (overactive spleen) may develop, with consequent thrombocytopenia and/or neutropenia.
  • Signs/symptoms of G6PD deficiency related to methemoglobinemia include: pallor, cyanosis, light-headedness, headache, palpitations, chest pain, and dyspnea. In very severe cases (methemoglobin fraction above 50%), dysrhythmias, seizures, coma, and even death can occur. At high levels of methemoglobinemia, blood appears to be chocolate brown in colour
  • Some persons with G6PD deficiency are elevated risk of sepsis (widespread infection of the blood) following severe trauma.

References and sources of more detailed information


Date: July 23, 2020
Revised: January 5, 2026


FOOTNOTES

1 Diagnosis is confirmed by measuring levels of the G6PD enzyme.
2 Persons with hemolytic anemia may need short-term treatment with oxygen and fluids to prevent hemodynamic shock, or, in severe cases of AHA where the rate of hemolysis is rapid, even blood transfusions. Blood transfusions are more likely to be required in children, particularly for favism, which can be life-threatening.
3 Severe methemoglobinemia is variously described by authorities as entailing methemoglobin fraction of 20% through 50%. Methemoglobin fraction of 70% is usually fatal.
4 While most patients/clients with G6PD deficiency do not exhibit significant hemolysis of red blood cells in the absence of a trigger, a minority experience ongoing, chronic hemolytic anemia even in the absence of an oxidative trigger.
5 Because certain antibiotics can trigger acute hemolytic anemia in patients/clients with G6PD deficiency, careful selection of antibiotic prophylaxis is warranted.
6 Medical references are inconsistent regarding “unsafe” versus “probably safe” drugs in persons with G6PD deficiency. This is a general, non-exhaustive list and may not apply to all G6PD-deficient individuals. According to some authorities, some medications previously thought to be unsafe are probably safe in usual therapeutic doses. Individual characteristics (e.g., degree of G6PD deficiency, dose, presence of infection, etc.) will influence actual safety or injury.
7 Penicillin and amoxicillin have also been rarely implicated in hemolysis in persons with G6PD-deficiency.
8 anti-helminthic agent = anti-parasitic drug for worms
9 The World Health Organization’s classes of G6PD deficiency are: I (congenital nonspherocytic hemolytic anemia and chronic hemolysis without exposure to oxidative stressors; rare, and tends to be in white males of Northern European background); II (severe deficiency, with 1-10% residual activity and intermittent oxidative stress-induced hemolysis; prototype is G6PD-Mediterranean); III (mild deficiency, with 10-60% residual activity and intermittent oxidative stress-induced hemolysis; most common type); IV (60-150% — normal activity, with no clinical sequelae); and V (> 150% — increased activity, with no clinical sequelae).
10 Case reports of NSAID-linked hemolytic anemia in G6PD-deficient persons exist in the medical literature.
11 According to some authorities, infection is probably the most common trigger inciting hemolysis in children who are G6PD deficient. Microbial triggers include E. coli, Rickettsia, cytomegalovirus, hepatitis A, hepatitis B, typhoid, beta-hemolytic streptococci, pneumonia, and those related to deep carious lesions and maxillofacial infections.
12 Jaundice is due to the presence of bilirubin from red blood cell breakdown.
13 Pallor (paleness) results from decreased oxygen-carrying capacity inherent in anemia and methemoglobinemia.
14 Cyanosis can result from methemoglobinemia.
15 G6PD enables red blood cells to convert carbohydrates into energy. Blockade of this enzymatic pathway in persons with G6PD deficiency results in production of methemoglobin and denatured hemoglobin, which leads to cell membrane alteration and hemolysis.
16 Methemoglobinemia (congenital or acquired MetHb) occurs when red blood cells (RBCs) contain methemoglobin at levels higher than 1%. Methemoglobin results from the presence of iron in RBCs in the ferric rather than the usual ferrous form. If the activity of G6PD is low, ferrous to ferric conversion occurs when RBCs are exposed to oxidizing triggers, resulting in methemoglobinemia (oxidized hemoglobin molecules), which impedes availability of oxygen to tissues.
17 It is uncommon for methemoglobinemia and acute hemolytic crisis to co-exist.
18 Because a female has two X chromosomes, certain disease traits on the affected X chromosome may be “masked” by a normal gene on the other X chromosome. By contrast, a male has only one X chromosome, and if he inherits an X chromosome that contains a disease gene (such as G6PD deficiency) he will develop (or have a greater likelihood of manifesting) the disease. Daughters of female carriers of an X-linked disorder have a 50% chance of being carriers themselves, whereas boys have a 50% chance of being affected.
19 G6PD deficiency is usually best managed by preventive measures. Individuals at elevated risk should be screened for the G6PD defect before being treated with oxidative drugs such as certain antibiotics, antimalarials, and other medications known to trigger hemolysis. In individuals who are G6PD-deficient, hemolytic anemia from known drugs or fava beans can be prevented, because exposure can be avoided. If hemolytic anemia is due to the use of a certain medication, its use should be discontinued under medical supervision. Similarly, if hemolytic anemia is caused by an underlying infection, the infection should be treated.
20 Acute hemolytic anemia from eating fava beans (favism) can be rapid. While favism can occur at any age, it occurs more often and severely in children. In severe cases, hypovolemic shock, or even heart failure, can occur.
21 Once the trigger is removed, the signs/symptoms of G6PD deficiency typically disappear quickly, usually within several weeks.


* Includes oral hygiene instruction, fitting a mouth guard, taking an impression, etc.
** Ontario Regulation 501/07 made under the Dental Hygiene Act, 1991. Invasive dental hygiene procedures are scaling teeth and root planing, including curetting surrounding tissue.