Class I Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency 

Class I glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most severe form of G6PD enzyme deficiency. The enzyme G6PD protects red blood cells from “oxidative stress.” In Class I, the enzyme activity is very low (typically under 10% of normal), so red blood cells are fragile and can break down even without obvious triggers. Because breakdown can happen again and again, people have chronic non-spherocytic hemolytic anemia (CNSHA)—a long-lasting form of anemia due to ongoing red cell destruction. This condition is inherited and most often affects males because the gene is on the X chromosome. Orpha+2ASH Publications+2

Class I G6PD deficiency is a very severe, inherited lack of a red-blood-cell enzyme called glucose-6-phosphate dehydrogenase. This enzyme’s job is to make NADPH, which keeps protective antioxidants (like glutathione) ready inside red blood cells. Without enough G6PD, red cells cannot handle “oxidative” stress from infections, some medicines, or certain chemicals/foods. In Class I, enzyme activity is <10% and people can have chronic, ongoing hemolytic anemia (red cells break too early) even without a trigger; jaundice and gallstones are common over time. The World Health Organization’s long-used scheme labels this as the most severe class; WHO also discussed an update to better match measured activity across variants. ASH Publications+2PMC+2

In 2022–2024, expert groups refined the WHO system that classifies G6PD variants by how much enzyme activity remains and how much hemolysis they cause. In the legacy WHO system, Class I means severe deficiency with chronic hemolysis (CNSHA). In an updated scheme, “Class A (<20% activity) maps to the old Class I and still means chronic hemolysis; milder classes cover acute, trigger-induced episodes or normal activity. Knowing this matters because it guides risk and testing. WHO+2Mayo Clinic Laboratories+2

Other names

Class I G6PD deficiency is also called “G6PD deficiency with chronic non-spherocytic hemolytic anemia (CNSHA),” “severe G6PD deficiency,” or “WHO Class I G6PD deficiency.” In newer descriptions, you may see “WHO Class A (<20% activity) with chronic hemolysis,” which corresponds to the same severe clinical picture. WHO+1

G6PD runs the first step of the pentose phosphate pathway, making NADPH, a molecule that keeps glutathione in its protective (reduced) form. Without enough G6PD, red blood cells cannot make enough NADPH, so oxidants from infections, certain foods, or drugs damage hemoglobin and the cell membrane. Damaged hemoglobin forms Heinz bodies, splenic macrophages “bite” those out (so you see bite cells on the smear), and the cells get destroyed early—causing anemia and jaundice. In Class I variants, the enzyme is so poor or unstable that hemolysis can be continuous, not just when something triggers it. ASH Publications+1

Types

Doctors talk about “types” in two ways. (1) By clinical class:

1. Legacy WHO Class I: <10% activity, chronic hemolysis (CNSHA).
2. Legacy WHO Class II: <10% activity, but mainly acute hemolysis with triggers.
3. Legacy WHO Class III: 10–60% activity, intermittent acute hemolysis.
4. Class IV–V: near-normal or increased activity; usually no disease.
   (2) By the 2022–2024 update: Four practical bands where “Class A (<20%)” corresponds to old Class I and still implies chronic hemolysis. Your report may use either system, so it’s useful to know how they line up. PMC+2PMC+2

There are also hundreds of named gene variants (mutations) that change G6PD structure or stability (for example, G6PD Union or G6PD Harilaou); many Class I variants cause a particularly unstable enzyme and thus chronic hemolysis from infancy onward. Genetic testing can name the variant, but the clinical class depends on enzyme activity and symptoms, not the name alone. MedlinePlus+1

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Causes

In Class I/CNSHA, hemolysis can occur without a clear trigger, but the following factors often worsen anemia.

1. Intercurrent infections. Viral or bacterial infections produce oxidants and fever; this can markedly worsen red-cell destruction. Prompt treatment lowers risk. NCBI+1

2. Fava beans (favism). Compounds in fava beans generate oxidative stress and can precipitate a crisis; this classic trigger is important worldwide. ASH Publications

3. Antimalarials (especially primaquine and tafenoquine). These medicines are strongly linked with hemolysis in G6PD deficiency and require prior screening or alternatives. NCBI+1

4. Dapsone. This antibiotic/anti-inflammatory is a well-known oxidative stressor for G6PD-deficient cells. ASH Publications

5. Sulfonamide antibiotics (e.g., sulfamethoxazole). Can trigger hemolysis; clinicians weigh risks and alternatives. ASH Publications

6. Nitrofurantoin. Used for urinary infections; frequently listed as a drug to avoid in G6PD deficiency. ASH Publications

7. Rasburicase. This uric acid–lowering drug produces hydrogen peroxide as it works and can cause severe hemolysis in G6PD deficiency. ASH Publications

8. Methylene blue. Sometimes used for methemoglobinemia; paradoxically dangerous in G6PD deficiency because it needs NADPH to work. ASH Publications

9. Phenazopyridine and nalidixic acid. Older urinary and antimicrobial agents noted to cause oxidative hemolysis. ASH Publications

10. High-dose aspirin and some NSAIDs. Large doses can be problematic; clinicians individualize advice. Verywell Health

11. Naphthalene (mothballs). Household exposure has triggered hemolysis in case reports. ASH Publications

12. Severe metabolic stress (e.g., diabetic ketoacidosis). Heightened oxidative load can exacerbate anemia. ASH Publications

13. Neonatal stressors (e.g., dehydration, infection). In affected newborns, stresses quickly raise bilirubin and hemolysis risk. MedlinePlus

14. Certain herbal or traditional remedies with oxidant properties. Local lists vary; caution is advised when contents are uncertain. ASH Publications

15. Severe acidosis or hypoxemia. These make red cells more vulnerable to oxidant injury. ASH Publications

16. Fever and inflammation (cytokine surge). Amplify oxidative species and can worsen baseline hemolysis. NCBI

17. Sulfa-containing combinations (e.g., sulfasalazine). Often placed on avoidance lists for G6PD-deficient patients. ASH Publications

18. Quinolone antibiotics (some agents). Older quinolones have been implicated; current practice assesses risk/benefit individually. ASH Publications

19. Henna/paraphenylenediamine exposures (rare). Oxidative dyes have been linked to hemolysis in reports. ASH Publications

20. The Class I variant itself (enzyme instability). Even without triggers, the intrinsic lack of G6PD activity leads to chronic hemolysis—this is the defining cause in Class I. Orpha+1

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Common symptoms

1. Pallor (pale skin, lips, nail beds). Caused by chronic anemia from ongoing red cell loss. ASH Publications

2. Fatigue and low energy. Fewer red cells mean less oxygen delivery to tissues. ASH Publications

3. Shortness of breath on exertion. The body works harder to deliver oxygen when anemic. ASH Publications

4. Fast heartbeat (palpitations). A compensatory response to anemia; sometimes picked up on exam. ASH Publications

5. Jaundice (yellow skin/eyes). Heme breakdown from hemolysis raises bilirubin levels. MedlinePlus

6. Dark or tea-colored urine. From hemoglobinuria or bilirubin pigments during hemolytic episodes. ASH Publications

7. Scleral icterus (yellow eyes). A visible sign of elevated bilirubin. MedlinePlus

8. Enlarged spleen (splenomegaly). The spleen clears damaged cells and can become enlarged with chronic work. ASH Publications

9. Gallstone-type pains (right upper abdomen). Chronic bilirubin turnover can form pigment gallstones over time. ASH Publications

10. Headaches and poor exercise tolerance. Typical of moderate to severe anemia. ASH Publications

11. In newborns: early jaundice. Jaundice appearing in the first days of life can be a clue. MedlinePlus

12. Irritability or dizziness. Symptoms related to reduced oxygen delivery. ASH Publications

13. Cold hands/feet. Sometimes reported with anemia and poor oxygen delivery. ASH Publications

14. Leg ulcers (rare, with long-standing hemolysis). Chronic hemolytic states can be associated with skin ulcers in some patients. ASH Publications

15. No symptoms between flares (in milder days). Even in Class I, day-to-day intensity varies; people may feel relatively well at times. ASH Publications

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Diagnostic tests

A) Physical examination

1. General appearance and vital signs. Doctors look for pallor, fatigue, fever (infection), fast heart rate, and rapid breathing—everyday clues to anemia or an acute hemolytic flare. ASH Publications

2. Skin and eye check for jaundice. Yellowing of skin and sclera suggests increased bilirubin from hemolysis. MedlinePlus

3. Abdominal exam for spleen size. Feeling an enlarged spleen supports chronic hemolysis. ASH Publications

4. Hydration and perfusion (capillary refill). Dehydration can worsen neonatal jaundice and anemia; refill time helps assess circulation. MedlinePlus

5. Newborn bilirubin risk assessment. In infants, early jaundice prompts screening and close follow-up to prevent bilirubin-related complications. MedlinePlus

B) “Manual” or bedside tests

6. Peripheral smear with special stains (Heinz bodies). A technician can use a supravital stain (e.g., crystal violet) to show Heinz bodies; “bite cells” and “blister cells” are typical in oxidative hemolysis. ASH Publications

7. Rapid G6PD screen (fluorescent spot test). A quick assay that shows whether NADPH is formed; if absent/dim, G6PD activity is low. Note: during acute hemolysis or soon after transfusion, results can appear falsely normal—so repeat later with a quantitative test. NCBI

8. Urine dipstick. May show blood/hemoglobin during a flare, supporting hemolysis. ASH Publications

9. Point-of-care hemoglobin. A finger-stick estimate helps confirm anemia quickly and track recovery. ASH Publications

C) Laboratory and pathology tests

10. Complete blood count (CBC) with reticulocyte count. Shows anemia and often an elevated retic count as the marrow tries to replace destroyed red cells. ASH Publications

11. Bilirubin (total and indirect), LDH, and haptoglobin. Indirect bilirubin and LDH rise; haptoglobin falls—classic hemolysis pattern. ASH Publications

12. Quantitative G6PD enzyme activity assay. The key diagnostic test; in Class I, levels are severely reduced. Best done away from an acute crisis to avoid false negatives. NCBI

13. Direct antiglobulin test (DAT/Coombs). Usually negative in G6PD deficiency, helping distinguish from immune hemolytic anemia. ASH Publications

14. Peripheral smear morphology (routine stain). “Bite” and “blister” cells support oxidative damage; combined with clinical story, this is very suggestive. ASH Publications

15. Genetic testing of the G6PD gene. Confirms the variant and can inform inheritance patterns and counseling; >200 variants are known. MedlinePlus

16. Newborn screening panels (where available). Some regions screen for G6PD deficiency in newborns to prevent severe jaundice and kernicterus. MedlinePlus

17. Urinalysis and plasma free hemoglobin. Support a hemolytic process during flares and help rule out other causes. ASH Publications

D) Electro-diagnostic / physiologic monitoring

18. Pulse oximetry and cardiopulmonary monitoring. During significant anemia, clinicians track oxygen saturation and heart rate to gauge severity and need for urgent care. ASH Publications

19. Electrocardiogram (ECG). Can document tachycardia or strain when anemia is severe; useful in symptomatic adults. ASH Publications

E) Imaging

20. Abdominal ultrasound (liver, gallbladder, spleen). Looks for splenomegaly and pigment gallstones that can occur with long-standing hemolysis; sometimes repeated if symptoms suggest complications. ASH Publications

Non-pharmacological

1. Trigger avoidance plan — Make and carry a personal list of “unsafe” oxidant drugs and chemicals; share it with all clinicians and pharmacists. Purpose: prevent hemolysis. Mechanism: avoiding high-risk oxidants such as primaquine, tafenoquine, dapsone, methylene blue, rasburicase/pegloticase prevents oxidative damage to G6PD-deficient RBCs. CPIC+1

2. Infection-fast action — Treat fevers and infections promptly (medical visit early). Purpose: reduce hemolysis from inflammatory oxidants. Mechanism: infections generate oxidative stress that can precipitate crises in G6PD deficiency. ASH Publications

3. Neonatal jaundice pathway — For newborns at risk, use the AAP 2022 nomograms for bilirubin checks, phototherapy, and timely exchange transfusion thresholds. Purpose: prevent bilirubin-induced brain injury. Mechanism: light therapy changes bilirubin into excretable forms; exchange removes bilirubin and sensitized cells. renaissance.stonybrookmedicine.edu+1

4. Hydration during crises — Oral fluids (or IV in hospital). Purpose: maintain kidney perfusion and help flush free hemoglobin. Mechanism: supports renal clearance to lower risk of pigment nephropathy during hemolysis. ASH Publications

5. Avoid fava beans and henna — Do not eat fava beans; avoid henna (lawsone) products on skin/hair—especially for infants. Purpose: remove well-documented triggers of severe hemolysis. Mechanism: vicine/convicine (fava) and lawsone (henna) generate strong oxidants. Medscape+1

6. Avoid naphthalene (mothballs) — Keep out of homes/closets; do not store baby clothes/diapers with mothballs. Purpose: prevent oxidant exposure. Mechanism: naphthalene causes oxidative hemolysis and sometimes methemoglobinemia, especially in G6PD-deficient infants. ATSDR+1

7. Medical alert ID — Wear a bracelet/card stating “Class I G6PD deficiency—high risk hemolysis.” Purpose: faster, safer emergency care. Mechanism: prompts clinicians to avoid high-risk drugs. CPIC

8. Vaccinations on time — Keep routine vaccines updated (e.g., influenza, pneumococcal as indicated). Purpose: fewer infections → fewer hemolytic episodes. Mechanism: lowers infection-triggered oxidative stress. ASH Publications

9. Folate-rich diet & rest — Support marrow recovery with good nutrition and rest during/after crises. Purpose: help the body make new RBCs. Mechanism: folate supports erythropoiesis; rest limits oxygen demand. (Folate tablets are covered under “drugs.”) NCBI

10. Safe-analgesic plan — Prefer acetaminophen or ibuprofen when needed (standard doses), avoiding aspirin in many situations. Purpose: pain/fever control without extra oxidative stress. Mechanism: these agents are not on high-risk lists for G6PD deficiency. NCBI

11. Sun- and heat-sensible routines — During acute anemia, avoid strenuous exertion and overheating. Purpose: reduce oxygen demand and symptoms. Mechanism: limits cardiac strain while hemoglobin is low. ASH Publications

12. Newborn screening & family testing — Where available, screen newborns and test at-risk relatives. Purpose: early identification to prevent crises. Mechanism: guides families to avoid triggers from day one. medi-guide.meditool.cn

13. Workplace/household audit — Replace oxidant exposures (e.g., aniline dyes/solvents; mothballs). Purpose: safer daily environment. Mechanism: lowers background oxidative load on RBCs. ATSDR

14. Travel malaria plan — If traveling to malaria areas, plan prophylaxis that is safe for your G6PD status; never start primaquine/tafenoquine without quantitative testing. Purpose: prevent malaria while avoiding hemolysis. Mechanism: testing prevents use of 8-aminoquinolines in deficient patients. CDC

15. Education session — Teach families the early signs of hemolysis (jaundice, dark urine, pallor, rapid heartbeat) and what to do. Purpose: earlier care. Mechanism: faster evaluation reduces complications. NCBI

16. Bilirubin monitoring at home (newborn) — Use scheduled bilirubin checks per AAP after discharge. Purpose: catch rebounds. Mechanism: follow-up decreases readmissions and kernicterus risk. American Academy of Pediatrics

17. Phototherapy quality — If admitted, ensure proper phototherapy intensity and eye protection for baby. Purpose: efficient bilirubin fall, safety. Mechanism: adequate irradiance speeds bilirubin photo-isomerization. AAFP

18. Anemia symptom diary — Track fatigue, exercise tolerance, urine color, scleral color. Purpose: pattern recognition. Mechanism: correlates exposures with symptoms for better avoidance. ASH Publications

19. Medication reconciliation at every visit — Review OTC and herbal products. Purpose: remove hidden oxidants (e.g., topical dyes, certain herbal/botanical quinones). Mechanism: intercepts risk before harm. CPIC

20. Genetic counseling — Discuss inheritance, female mosaicism, and family planning. Purpose: informed choices and screening of partners/infants. Mechanism: X-linked transmission explains risk to sons/daughters. ASH Publications

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Drug treatments used in management

There is no disease-modifying medicine that “fixes” G6PD deficiency today. Medicines are used to (1) treat complications, (2) treat infections safely, and (3) support red-cell production—while avoiding high-risk oxidant drugs.

1. Folic acid — 1 mg orally daily (typical). Purpose: support new RBC formation in chronic hemolysis. Mechanism: cofactor for DNA synthesis in erythropoiesis; long-term supplementation is standard in chronic hemolysis. Side effects: rare GI upset. NCBI

2. Acetaminophen (paracetamol) — 500–1000 mg every 6–8 h (max per local guidance). Purpose: pain/fever. Mechanism: central COX inhibition; not a high-risk oxidant in G6PD. Side effects: hepatotoxicity at high doses—respect maximum. NCBI

3. Ibuprofen — 200–400 mg every 6–8 h with food. Purpose: pain/fever. Mechanism: peripheral COX inhibition; not on high-risk G6PD lists. Side effects: GI upset, renal risk in dehydration—avoid during severe hemolysis with kidney stress. NCBI

4. Penicillin-class antibiotics (e.g., amoxicillin 500 mg q8h) when clinically indicated. Purpose: treat bacterial infections (a common hemolysis trigger). Mechanism: β-lactam wall inhibition; not high-risk oxidants. Side effects: allergy, GI upset. NCBI

5. Cephalosporins (e.g., cephalexin 500 mg q6–8h) when indicated. Purpose/mechanism: as above; generally safe regarding G6PD hemolysis. Side effects: as class. NCBI

6. Azithromycin — 500 mg day 1; then 250 mg daily days 2–5, if indicated. Purpose: respiratory/atypical infections. Mechanism: macrolide protein-synthesis inhibition; not on high-risk G6PD lists. Side effects: GI upset, QT risk. NCBI

7. Ceftriaxone (parenteral) for serious infections. Purpose: sepsis/pneumonia per guidelines. Mechanism: β-lactam; not a high-risk oxidant. Side effects: biliary sludging, allergy. NCBI

8. Chloroquine (when indicated for malaria according to susceptibility). Purpose: malaria treatment/preventing relapse in specific settings when 8-aminoquinolines are unsafe. Mechanism: antiplasmodial; does not require hemolysis-provoking activity; dosing per guidelines. Side effects: GI upset, retinal toxicity with long use. CDC

9. Atovaquone-proguanil (when indicated). Purpose: malaria treatment in certain cases. Mechanism: mitochondrial & folate-pathway inhibition; not high-risk for G6PD hemolysis. Side effects: GI upset; avoid in severe renal impairment. CDC

10. Artemether-lumefantrine (indications per malaria guidance). Purpose: malaria treatment option. Mechanism: endoperoxide antimalarial; not a classic hemolysis trigger in G6PD deficiency. Side effects: headache, GI upset. CDC

11. Erythropoiesis-stimulating agents (selected cases) — dosing individualized. Purpose: support RBC production if appropriate (e.g., coexisting renal anemia). Mechanism: mimics EPO to stimulate marrow. Side effects: thrombosis, hypertension—specialist use only. ASH Publications

12. Folic acid “rescue” during crises — Sometimes increased to 1–5 mg daily short-term. Purpose: rapid marrow support. Mechanism: replenish folate used by reticulocytosis. Side effects: minimal; avoid masking B12 deficiency. NCBI

13. Proton-pump inhibitor (short course if needed) — e.g., omeprazole 20 mg daily. Purpose: GI protection if ibuprofen is used briefly. Mechanism: acid suppression. Side effects: headache; use only if indicated. NCBI

14. Antiemetics (ondansetron 4–8 mg) if hemolysis causes nausea. Purpose: hydration adherence. Mechanism: 5-HT3 antagonism. Side effects: constipation, QT risk. ASH Publications

15. Topical/local anesthetics for procedures (standard doses). Purpose: comfort for venipuncture/lines. Mechanism: sodium channel blockade; not hemolysis triggers. Side effects: rare methemoglobinemia with benzocaine—avoid high-risk agents; use lidocaine as directed. ASH Publications

16. Safe laxatives (PEG 3350). Purpose: comfort if iron (rarely needed) causes constipation. Mechanism: osmotic. Side effects: bloating. (Iron is not routinely indicated in chronic hemolysis unless iron deficiency is proven.) ASH Publications

17. Vitamin B12 (if deficient) — 1000 µg PO daily or IM protocol. Purpose: correct megaloblastic component. Mechanism: DNA synthesis. Side effects: rare acne/rash. ASH Publications

18. Antibiotic stewardship — choose non-oxidant options first; avoid nitrofurantoin, dapsone, primaquine, tafenoquine, methylene blue, rasburicase/pegloticase in G6PD deficiency. Purpose: treat safely. Mechanism: prevent oxidant hemolysis. Side effects: n/a—it’s a safety rule. CPIC

19. Transfusion medicine (packed RBCs) — procedure, but listed here because it uses blood products. Purpose: treat severe anemia. Mechanism: supplies healthy RBCs; thresholds per clinical judgment. Risks: transfusion reactions; hospital only. ASH Publications

20. Phototherapy (newborn) — again a device therapy, included here because it is frontline neonatal “treatment.” Purpose: lower bilirubin. Mechanism: photo-isomerization increases excretion. Risks: dehydration, temperature instability; hospital protocol. renaissance.stonybrookmedicine.edu

Absolutely avoid high-risk oxidants in G6PD deficiency: primaquine, tafenoquine, dapsone, methylene blue, rasburicase, pegloticase, toluidine blue (others are medium/low risk and require context). Always perform quantitative G6PD testing before 8-aminoquinolines. CPIC PGx Files+1

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Dietary molecular supplements

Supplements have limited or mixed evidence in Class I G6PD deficiency. Discuss with your clinician before use.

1. Folate (vitamin B9) — 1 mg/day typical. Function: cofactor for DNA synthesis; supports marrow during chronic hemolysis. Mechanism: aids RBC production. Caution: do not mask B12 deficiency. NCBI

2. Vitamin B12 — if deficient; typical oral 1000 µg/day. Function: erythropoiesis. Mechanism: coenzyme for nucleotide synthesis. Caution: check levels first. ASH Publications

3. Vitamin E (antioxidant) — evidence inconsistent for hemolysis reduction. Function/mechanism: lipid antioxidant protecting RBC membranes. Caution: high-dose bleeding risk; benefit uncertain in G6PD. ASH Publications

4. Vitamin C — avoid high doses (can be pro-oxidant); if used, stay within diet/RDA. Function: antioxidant at physiologic levels. Mechanism: redox cofactor. Caution: large doses have triggered hemolysis/methemoglobinemia in case reports. ASH Publications

5. Riboflavin (B2) — cofactor for redox enzymes. Mechanism: supports glutathione reductase activity. Evidence: limited; safe at RDA. ASH Publications

6. N-acetylcysteine (NAC) — theoretical glutathione precursor benefit. Evidence: limited/experimental in G6PD. Caution: discuss with clinician. PMC

7. Coenzyme Q10 — antioxidant role; evidence in hemolysis is weak. Mechanism: electron transport and redox buffering. Caution: interactions (warfarin). PMC

8. Omega-3 fatty acids — anti-inflammatory; no direct G6PD data. Mechanism: membrane effects. Caution: bleeding risk with high doses. PMC

9. Selenium — part of glutathione peroxidase; evidence sparse. Caution: toxicity if excessive. PMC

10. Zinc — general immune support; no hemolysis-specific benefit proven. Caution: copper deficiency with excess zinc. PMC

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Immunity-booster / regenerative / stem-cell drug

1. Gene therapy (ex vivo HSC editing/gene addition) — Early lab/animal work shows feasibility of adding/correcting G6PD in hematopoietic stem cells; human clinical application remains investigational. Mechanism: restore enzyme in RBC lineage. PMC

2. Prime editing/CRISPR correction of specific variants (e.g., Viangchan) — Recent iPSC and cell-line studies show precise correction with promising efficiency; still preclinical. Mechanism: direct DNA correction of pathogenic variant. Nature

3. In vivo HSC editing (general platform) — Emerging technologies target HSCs in vivo; not yet a therapy for G6PD but relevant to future possibilities. Mechanism: edits stem cells without transplant. CRISPR Medicine

4. Pharmacologic chaperones for G6PD — Concept: stabilize misfolded G6PD to raise activity; proposed for bilirubin toxicity reduction; still experimental. Mechanism: small molecules bind/enhance enzyme stability. PubMed

5. Nrf2 pathway activators/HDAC modulators — Hypothesis: upregulate antioxidant defenses or residual G6PD; preclinical discussion only. Mechanism: boost cellular redox capacity. ScienceDirect

6. Cell/gene therapy learnings from other anemias — Success in thalassemia/SCD informs future G6PD approaches but not yet applied clinically. Mechanism: gene-corrected HSCs engraft and produce healthier RBCs. PMC

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Procedures/surgeries used for complications

1. Exchange transfusion (newborn) — Urgent in severe hyperbilirubinemia per AAP/CPS thresholds to prevent encephalopathy. Why: rapidly lowers bilirubin and replaces RBCs. renaissance.stonybrookmedicine.edu+1

2. Laparoscopic cholecystectomy — For symptomatic pigment gallstones from chronic hemolysis (biliary colic, cholecystitis). Why: definitive stone management; laparoscopy is standard for symptomatic disease. CCJM+1

3. ERCP — For choledocholithiasis (common bile duct stones) causing jaundice or pancreatitis. Why: endoscopic stone removal when needed. PMC

4. Splenectomy (rarely) — Sometimes considered in selected chronic nonspherocytic hemolysis, but benefit is limited and evidence is weak; not routine. Why: may reduce splenic RBC destruction in a subset; risks must be weighed. ASH Publications

5. Central venous access — For repeated transfusions in severe chronic anemia or exchange transfusions in neonates. Why: reliable access for life-saving blood products. ASH Publications

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Preventions

1. Quantitative G6PD testing before primaquine/tafenoquine; avoid if deficient. CDC

2. Avoid high-risk oxidant drugs (primaquine, tafenoquine, dapsone, methylene blue, rasburicase/pegloticase, toluidine blue). CPIC PGx Files

3. Avoid fava beans and henna (lawsone). Medscape+1

4. Keep mothballs (naphthalene) out of the home; never store diapers/clothes with them. ATSDR

5. Treat infections early; seek care for fever. ASH Publications

6. Keep vaccines updated (per age/condition). ASH Publications

7. Carry a medication list/alert ID. CPIC

8. Plan safe malaria prophylaxis if traveling. CDC

9. Use safe analgesics (acetaminophen/ibuprofen) as needed—within standard limits. NCBI

10. Newborns: follow AAP bilirubin screening and follow-up. American Academy of Pediatrics

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When to see doctors

• Immediately (ER): rapidly rising jaundice, very dark (“tea-colored”) urine, severe pallor, extreme fatigue or shortness of breath, fast heart rate at rest, confusion, or any signs of severe infection. These may signal an acute hemolytic crisis. ASH Publications

• Newborn: any jaundice in first 24 h, poor feeding, lethargy, or bilirubin near treatment thresholds. renaissance.stonybrookmedicine.edu

• Soon (clinic): fever, new medication start, travel planning to malaria regions, pregnancy planning, or recurrent abdominal pain suggesting gallstones. CDC+1

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What to eat and what to avoid

1. Eat a balanced diet with leafy greens and folate-rich foods to support RBC production. NCBI

2. Avoid fava beans entirely. Medscape

3. Avoid henna products (including on infants). Frontiers

4. Avoid mothballs in the home; no food stored near them. ATSDR

5. Stay hydrated, especially during illness. ASH Publications

6. Keep caffeine and alcohol moderate (general health); avoid dehydration. ASH Publications

7. No special “G6PD diet” is required beyond trigger avoidance and good nutrition. ASH Publications

8. Use caution with herbal products/dyes; check ingredients. CPIC

9. If anemic, small frequent meals to maintain energy. ASH Publications

10. Discuss iron only if deficiency is proven (chronic hemolysis often does not need iron). ASH Publications

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FAQs

1. What makes Class I special? It causes chronic hemolysis with enzyme activity <10%—more severe than other classes. PMC

2. Is there a cure? Not yet; gene therapy is experimental. Care focuses on trigger avoidance and supportive treatment. PMC

3. Can women be affected? Yes—due to X-inactivation (mosaicism), some females have significant deficiency. ASH Publications

4. How is it diagnosed? By quantitative enzyme assay (plus genotype in some cases); avoid testing during acute hemolysis. medi-guide.meditool.cn

5. Why do newborns need special care? They are at higher risk of dangerous jaundice; AAP 2022 gives safer thresholds and follow-up rules. renaissance.stonybrookmedicine.edu

6. Are acetaminophen or ibuprofen safe? At normal doses they are generally considered acceptable; avoid aspirin unless directed. NCBI

7. Which antimalarials are a problem? Primaquine/tafenoquine—require quantitative G6PD testing first. CDC

8. Do all antibiotics cause hemolysis? No. Choose non-oxidant options (many β-lactams/macrolides are fine) and avoid dapsone/nitrofurantoin. CPIC PGx Files

9. Can supplements help? Folate helps RBC production; others have limited evidence—discuss first. NCBI

10. Why gallstones? Chronic hemolysis increases bilirubin → black pigment stones over time. CCJM

11. Is splenectomy helpful? Rarely and selectively; not routine for G6PD deficiency. ASH Publications

12. Can hair dye/henna trigger hemolysis? Yes—henna (lawsone) can, especially in infants—avoid. Frontiers

13. Are mothballs dangerous? Yes—naphthalene can cause severe hemolysis; keep out of the home. ATSDR

14. How do I prepare for surgery/dental work? Tell the team; carry your alert card; review medications and dyes (e.g., methylene blue is unsafe). CPIC PGx Files

15. Can I live a normal life? Yes—most complications are preventable with education, trigger avoidance, and prompt care for infections/jaundice. ASH Publications

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 17, 2025.

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