Glucose-6-phosphate dehydrogenase deficiency

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

G6PD deficiency was first discovered more than 50 years ago. Prisoner volunteers were given primaquine and some of them developed hemolytic anemia. G6PD deficiency may be classified to into 5 subtypes. It is understood that G6PD deficiency is the result of reduced Glucose-6-phosphate dehydrogenase enzyme levels. G6PD deficiency is an X-linked disorder. Glucose-6-phosphate dehydrogenase enzyme oxidizes glucose-6-phosphate to 6-phosphogluconolactone in pentose phosphate pathway ( HMP shunt). The most common cause of G6PD deficiency is due to genetic disorder. Less common cause of G6PD deficiency include neutrophil dysfunction. G6PD deficiency is affecting 400 million people worldwide. patients of all age groups may develop favism, but more often and severe in children. African, Middle Eastern and South Asian people are affected the most. Men are more commonly affected by G6PD deficiency. Common risk factors in the development of G6PD deficiency include some foods such as fava beans, some medications and infections. The symptoms of G6PD deficiency typically develop after exposure to some foods and medications. Common complications of G6PD deficiency include acute hemolytic anemia and neonatal jaundice.Diagnostic study of choice for G6PD deficiency include quantitative laboratory assay, Beutler fluorescent spot test and DNA testing for mutated genes. The mainstay of treatment for G6PD deficiency is avoidance of the foods such as fava beans and drugs that cause hemolysis. Pharmacologic medical therapy is recommended among patients with chronic hemolysis. Blood transfusion can be considered in acute phase of hemolysis.

G6PD deficiency was first discovered more than 50 years ago. Prisoner volunteers were given primaquine and some of them developed hemolytic anemia.

G6PD deficiency may be classified to into 5 subtypes. Class I: Severe deficiency with chronic hemolytic anemia. Class 2: Severe deficiency with intermittent hemolysis. Class III: Moderate deficiency, hemolysis with significant oxidant stress. Class IV: No enzyme deficiency or hemolysis. Class V: Increased enzyme activity.

It is understood that G6PD deficiency is the result of reduced Glucose-6-phosphate dehydrogenase enzyme levels. G6PD deficiency is an X-linked disorder. Glucose-6-phosphate dehydrogenase enzyme oxidizes glucose-6-phosphate to 6-phosphogluconolactone in pentose phosphate pathway ( HMP shunt). Glucose-6-phosphate dehydrogenase enzyme also reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. NADPH is an important cofactor in glutathione metabolism against oxidative injury in RBC. In G6PD deficiency, oxidative stresses can denature hemoglobin and intravascular hemolysis in RBC can happen. The gene G6PD is located in the distal long arm of the X chromosome at the Xq28 locus. G6PD B, is the wild type or normal. On microscopic histopathological analysis, Heinz bodies can be visualized as a result of denatured hemoglobin in peripheral blood smears with supravital staining.

The most common cause of G6PD deficiency is due to genetic disorder. Less common cause of G6PD deficiency include neutrophil dysfunction.

G6PD deficiency is affecting 400 million people worldwide. patients of all age groups may develop favism, but more often and severe in children. African, Middle Eastern and South Asian people are affected the most. Men are more commonly affected by G6PD deficiency.

Common risk factors in the development of G6PD deficiency include some foods such as fava beans, some medications and infections.

G6PD deficiency screening in neonates is done routinely in some regions with high incidence. Screening is done before giving oxidant medication to high risk patients.

The symptoms of G6PD deficiency typically develop after exposure to some foods and medications. Common complications of G6PD deficiency include acute hemolytic anemia and neonatal jaundice.

Diagnostic study of choice for G6PD deficiency include quantitative laboratory assay, Beutler fluorescent spot test and DNA testing for mutated genes.

The majority of patients with G6PD deficiency are asymptomatic. Common symptoms of G6PD include nausea, back pain, headache, chills. Less common symptoms include acute renal failure and shortness of breath.

Patients with G6PD deficiency usually appear normal. Physical examination of patients with G6PD deficiency is usually remarkable for Jaundice in hemolysis, Abdominal tenderness in the right upper abdominal quadrant because of hyperbilirubinemia.

Laboratory findings consistent with the diagnosis of G6PD deficiency include hemoglobinuria, neonatal hyperbilirubinemia, elevated Lactate dehydrogenase in hemolysis

There are no ECG findings associated with G6PD deficiency.

There are no x-ray findings associated with Glucose-6-phosphate dehydrogenase deficiency.

There are no CT scan findings associated with Glucose-6-phosphate dehydrogenase deficiency.

There are no MRI findings associated with Glucose-6-phosphate dehydrogenase deficiency.

There are no echocardiography/ultrasound findings associated with Glucose-6-phosphate dehydrogenase deficiency.

There are no other imaging findings associated with Glucose-6-phosphate dehydrogenase deficiency.

Other diagnostic studies for G6PD deficiency include CBC, Lactate dehydrogenase, Haptoglobin, Urinalysis, Peripheral blood smear.

The mainstay of treatment for G6PD deficiency is avoidance of the foods such as fava beans and drugs that cause hemolysis. Pharmacologic medical therapy is recommended among patients with chronic hemolysis. Blood transfusion can be considered in acute phase of hemolysis.

Surgical intervention is not recommended for the management of G6PD deficiency. Splenectomy may be considered in rare cases.

Effective measures for the primary prevention of G6PD deficency include avoiding triggers.

Effective measures for the secondary prevention of G6PD deficiency include avoiding triggers.

Case #1

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

G6PD deficiency was first discovered more than 50 years ago. Prisoner volunteers were given primaquine and some of them developed hemolytic anemia

• G6PD deficiency was first discovered more than 50 years ago.^[1]

• The association between primaquine and discovery of G6PD deficiency was made during a study at Illinois State Penitentiary. Prisoner volunteers were given primaquine and some of them developed hemolytic anemia.^[2]
• Numerous soldiers developed hemolytic anemia after taking primaquine to prevent relapsing infection by plasmodium vivax during Korean War. Most of them are from North African and Mediterranean.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

G6PD deficiency may be classified to into 5 subtypes and gives some approximation of the magnitude of hemolysis an individual may incur in the setting of an oxidative stress.

G6PD deficiency may be classified according to World Health Organization into 5 subtypes: ^[1][2]

• Class I: Severe deficiency (<10% activity) with chronic hemolytic anemia.
• Class II: Severe deficiency (<10% activity), with intermittent hemolysis. G6PD Mediterranean deficiency is a class II deficiency.
• Class III: Moderate deficiency (10-60% activity), hemolysis with significant oxidant stress. G6PD A- deficiency is a class III deficiency.
• Class IV: No enzyme deficiency or hemolysis, no clinical sequelae. it has G6PD B, normal wild-type enzyme
• Class V: Increased enzyme activity (more than twice normal), no clinical sequela

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• Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

It is understood that G6PD deficiency is the result of reduced Glucose-6-phosphate dehydrogenase enzyme levels. G6PD deficiency is an X-linked disorder. Glucose-6-phosphate dehydrogenase enzyme oxidizes glucose-6-phosphate to 6-phosphogluconolactone in pentose phosphate pathway ( HMP shunt). Glucose-6-phosphate dehydrogenase enzyme also reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. NADPH is an important cofactor in glutathione metabolism against oxidative injury in RBC. In G6PD deficiency, oxidative stresses can denature hemoglobin and intravascular hemolysis in RBC can happen. The gene G6PD is located in the distal long arm of the X chromosome at the Xq28 locus. G6PD B, is the wild type or normal. On microscopic histopathological analysis, Heinz bodies can be visualized as a result of denatured hemoglobin in peripheral blood smears with supravital staining.

The normal physiology of G6PD deficiency can be understood as follows:

• It is understood that G6PD deficiency is the result of reduced Glucose-6-phosphate dehydrogenase enzyme levels. G6PD deficiency is an X-linked disorder. It is the most common enzymatic disorder of red blood cells. Glucose-6-phosphate dehydrogenase enzyme oxidizes glucose-6-phosphate to 6-phosphogluconolactone in pentose phosphate pathway ( HMP shunt). Glucose-6-phosphate dehydrogenase enzyme also reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. NADPH is an important cofactor in glutathione metabolism against oxidative injury in RBC. Reduced glutathione (GSH) convert to oxidized glutathione (GSSG) by glutathione peroxidase enzyme that prevents oxidant accumulation. Glutathione reductase catalyzes the reduction of GSSG to GSH by NADPH. In G6PD deficiency, oxidative stresses can denature hemoglobin and intravascular hemolysis in RBC can happen. Infection, some medications and foods with high level of convicine, vicine, divicine and isouramil such as fava beans can cause oxidative stress. The spleen is the organ for sequestration damaged RBC. The hemoglobin is metabolized to bilirubin and cause jaundice.

G6PD deficiency is transmitted in x-linked disorder pattern. The gene G6PD is located in the distal long arm of the X chromosome at the Xq28 locus. ^[1]

Heterozygous women are usually normal because of lyonization ( X innactivation)^[2]

G6PD B, is the wild type or normal. G6PD has 400 variant enzymes. ^[3] Caucasians, Asians and majority of blacks has G6PD B.

G6PD A+: In Africa, in 20-30 percent of black. In this variant, asparagine is substitued for aspartate, at amino acid 126. ^[4] It has normal enzyme activity.

The development of G6PD deficency is the result of missense point mutations and also a few deletions. ^[5]

• G6PD A+:In Africa, in 20-30 percent of black. In this variant, asparagine is substitued for aspartate, at amino acid 126. ^[4] It has normal enzyme activity.
• G6PD A-: Cause primaquine sensitivity in blacks.
• G6PD mediterranean variant: Single base substitution (C—>T) at nucleotide 563 ^[6]
• G6PD variants in Asia:
  • In China: G6PD Canton (1376 G—>T), G6PD Kaiping (1388 G—>A), G6PD Gaohe (95 G—>A)^[7]
  • In Southeast Asia: G6PD Mahidol (487G—>A)

• G6PD A− and G6PD Mediterranean has protective effect against Plasmodium falciparum and Plasmodium vivax malaria. ^[8]
• G6PD deficency is a risk factor of male neonatal sepsis^[9]

On gross pathology,there are no characteristic findings of G6PD deficiency.

On microscopic histopathological analysis, Heinz bodies can be visualized as a result of denatured hemoglobin in peripheral blood smears with supravital staining. (Heinz body prep).^[10]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2] [3]

The most common cause of G6PD deficiency is due to genetic disorder. Less common cause of G6PD deficiency include neutrophil dysfunction.

Common cause of G6PD deficiency may include:

• Genetic: G6PD deficiency is an X-linked disorder

Less common causes of G6PD deficiency include:

• Neutrophil dysfunction in severe G6PD deficiency ( <20 percent activity ) ^[1]

The gene G6PD is located in the distal long arm of the X chromosome at the Xq28 locus. G6PD B, is the wild type or normal.^[2]

The development of G6PD deficency is the result of missense point mutations and also a few deletions^[3]

Cardiovascular	No underlying causes
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	X-linked disorder
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

List the causes of the disease in alphabetical order:

• Genitic
• Neutrophil dysfunction

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

G6PD deficiency is affecting 400 million people worldwide. atients of all age groups may develop favism, but more often and severe in childern. African, Middle Eastern and South Asian people are affected the most. Men are more commonly affected by G6PD deficiency.

• G6PD deficiency is affecting 400 million people worldwide. ^[1]

• G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990^[2]

• Patients of all age groups may develop favism (acute hemolytic anemia from eating fava beans ), but more often and severe in childern.

• African, Middle Eastern and South Asian people are affected the most.

• Men are more commonly affected by G6PD deficiency than women, because it is an X-linked recessive disorder.

• The majority of G6PD deficiency cases are reported in African, Middle Eastern and South Asian people. ^[3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

Common risk factors in the development of G6PD deficiency include some foods such as fava beans, some medications and infections.

Common risk factors in the development of G6PD deficiency include some foods such as fava beans, some medications and infections.

• Common risk factors in the development of G6PD include:
  • Foods such as fava beans in G6PD mutation carriers
  • Medications ^[1]
    • Aspirin
    • Antimalarials: quinine, primaquine, pamaquine, and chloroquine
    • Sulfonamides: mafenide, sulfanilamide, sulfamethoxazole
    • Thiazolesulfone
    • Methylene blue
    • Analgesics: phenazopyridine and acetanilide
    • Rasburicase
    • Some non-sulfa antibiotics such as furazolidone, isoniazid, dapsone, nalidixic acid, nitrofurantoin).
    • High dose vitamin C
  • Bacterial, viral and rickettsial infection
  • Some chemicals: Hanna in tattos and hair dyes^[2]

• Less common risk factors in the development of G6PD include:
  • Moth balls (naphthalene)
  • Diabetic ketoacidosis^[3]
  • Amyl nitrite or isobutyl nitrite in RUSH ( sexual enhancement drug)^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

G6PD defeciency screening in neonates is done routinly in some regions with high incidence.

• G6PD defeciency screening in neonates is done routinly in some regions with high incidence. ^[1]
• Screening test is quantitative laboratory assay for G6PD enzyme activity.
• Screening is done before giving oxidant medication to high risk patients.
• There is insufficient evidence to recommend routine screening for G6PD deficiency.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

The symptoms of G6PD deficiency typically develop after exposure to some foods and medications. Common complications of G6PD deficiency include acute hemolytic anemia and neonatal jaundice.

• The symptoms of G6PD deficiency typically develop after exposure to some foods and medications.

• Common complications of G6PD deficiency include:^[1]
  • Acute hemolytic anemia
  • Neonatal jaundice
  • Acute kidney failure

• Prognosis is generally good.^[2]

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