Updated: 2/8/2019

G6PD Deficiency

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Snapshot
  • A 13-year-old African-American boy presents to his pediatrician for jaundice. He states that he had tried some new Mediterranean food at school today. A day later, he felt fatigued and tired easily after minimal activity and reported back pain. On physical exam, he has scleral icterus. His hemoglobin was found to be 8 g/dL with increased reticulocyte count, increased indirect bilirubin, and decreased haptoglobin. He is given 1 unit of blood.
Introduction
  • Clinical definition
    • glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that causes an intrinsic hemolytic anemia
  • Epidemiology
    • prevalence
      • 7.1% worldwide
      • most common enzyme disorder of erythrocytes
    • demographics
      • more severe in males than females
      • common in areas where malaria is endemic
        • sub-Saharan Africa
        • Middle East
        • Southeast Asia
        • Mediterranean regions
        • Pacific islands
  • Pathophysiology
    • G6PD affects the pentose phosphate (hexose monophosphate) pathway
      • generates nicotinamide dinucleotide phosphate (NADPH), which protects red blood cells against oxidative stress 
      • in red blood cells (without mitochondria), this pathway is the only source of NADPH
      • acute hemolytic anemia following exposure to oxidative stressors  
        • primaquine
        • dapsone
        • nitrofurantoin
        • sulfa drugs
        • infections
        • fava bean ingestion
      • oxidative stressors cause
        • rapid depletion of reduced glutathione resulting in
          • precipitation of hemoglobin (manifested as Heinz bodies)
          • erythrocyte membrane damage, both extravascular and intravascular hemolysis
      • G6PD deficiency thought to decrease risk of severe malaria
  • Genetics 
    • inheritance pattern
      • X-linked
    • mutations
      • G6PD gene encoding the G6PD enzyme
  • Prognosis
    • natural history of disease
      • typically asymptomatic until exposed to oxidative stressors
Presentation
  • Symptoms
    • primary symptoms
      • neonatal hyperbilirubinemia on day 2-4
      • acute hemolytic anemia following exposure to precipitants, typically within 24-72 hours after ingestion
        • fatigue
        • jaundice
        • dark urine
        • back pain
  • Physical exam
    • inspection
      • jaundice
        • kernicterus is rare
Studies
  • Labs
    • complete blood count and reticulocyte count
    • peripheral smear 
      • bite cells
      • Heinz bodies
    • hemolysis labs
      • ↑ indirect bilirubin
      • ↓ haptoglobin
      • ↑ lactate dehydrogenase
    • urine 
      • hemoglobinuria
  • G6PD activity assays
    • indications
      • screening
    • fluorescent spot test
      • most sensitive
    • methemoglobin reduction test
  • Quantitative assays
    • indications
      • confirmation of diagnosis
        • a normal G6PD level immediately after hemolysis does not rule out G6PD deficiency
    • spectrophotometry analysis
    • molecular diagnosis (DNA analysis)
Differential
  • Gilbert syndrome
    • jaundice at birth (rather than delayed onset of jaundice)
    • normal G6PD enzyme activity
  • Hereditary spherocytosis
    • spherocytosis seen on peripheral blood smear

Disease
Peripheral Smear Findings
Thalassemia
  • Target cells
B12 deficiency
  • Hypersegmented neutrophils
Folic acid deficiency
G6PD deficiency
  • Heinz bodies and bite cells
Asplenia
  • Howell-Jolly bodies
Mechanical destruction
  • Schistocytes
Microangiopathic hemolytic anemia
Hereditary spherocytosis
  • Spherocytes
Autoimmune hemolysis

Treatment
  • Conservative
    • avoid oxidative stressors
  • Medical
    • blood transfusion
      • indications
        • if hemoglobin < 7 g/dL without hemolysis
        • if hemoglobin < 9 g/dL with hemolysis
    • phototherapy
      • indication
        • neonatal hyperbilirubinemia
Complications
  • Recurrence of acute hemolysis
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.HE.4691) A 5-year-old African American boy is brought into the emergency department by his mother. The mother states that the boy was diagnosed with a urinary tract infection by his PCP and provided with medications a few days ago. Today, he started having abdominal pain and shortness of breath. On exam, the patient has normal vitals, but has mild jaundice and states that he is short of breath. His mother states that her brother had had a similar episode when he was treated for malaria. The child's CBC is significant for a hemoglobin of 8.7 and his MCV is 90. Figure A shows the peripheral smear. Coombs test is negative. What is the most likely diagnosis? Review Topic

QID: 107611
FIGURES:
1

Iron deficiency anemia

0%

(0/0)

2

Autoimmune hemolytic anemia

0%

(0/0)

3

Sickle cell anemia

0%

(0/0)

4

Thalassemia

0%

(0/0)

5

G6PD deficiency

0%

(0/0)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M2.HE.34) A 44-year-old obese African-American male presents to clinic with complaints of 3 days of fatigue and dark urine. He has had several similar episodes since birth, all of which resolved spontaneously. He has a 5-year history of poorly controlled type II diabetes mellitus and was started on glipizide one week ago. Prior to the episode, he felt well without any upper respiratory or gastrointestinal symptoms. He predominantly eats fast food, although he tried a new Lebanese restaurant about one month ago. Which of the following is the most likely cause of this patient's symptoms? Review Topic

QID: 104359
1

Viral Infection

7%

(5/76)

2

Bacterial Infection

4%

(3/76)

3

Food

33%

(25/76)

4

Medication

46%

(35/76)

5

Idiopathic

8%

(6/76)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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