Updated: 7/24/2018

G6PD Deficiency

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Questions
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Snapshot
  • A 25-year-old man with Mediterranean ancestry presents with jaundice. He also reports being unusually tired and believes this may be due to his recent recovery from  mononucleosis. He was found to be anemic with a hemoglobin of 9 g/dL. His peripheral blood smear revealed bite cells and Heinz bodies.
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
      • this 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
        • 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 is 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
    • jaundice
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
    • indication
      • 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
Differential
  • Gilbert syndrome
    • jaundice at birth (rather than delayed onset of jaundice)
    • normal G6PD enzyme activity
  • Hereditary spherocytosis
    • spherocytosis seen on peripheral blood smear
Treatment
  • Conservative
    • avoid oxidative stressors
  • Medical
    • blood transfusion
      • indication
        • if severe
Complications
  • Recurrence of acute hemolysis
 

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Questions (5)
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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(M1.HE.72) A 21-year-old African American male with a history of HIV presents to the clinic with a complaint of cough, shortness of breath, and fever that has seemed to slowly progress over the past week. Upon questioning, he admits to not being able to take his HAART regimen due to recently losing his health insurance. Concerned, the physician pursues a full workup. The patient is found to have a pneumonia caused by a gram-positive, acid fast aerobe, and the physician prescribes the appropriate medication. After 1 day of taking the medication, the patient returns to the physician with complaints of severe weakness and dark colored urine. On exam, the physician notes that the patient is jaundiced and has splenomegaly. Which figure demonstrates the mode of inheritance of this patient's genetic condition? Review Topic

QID: 106539
FIGURES:
1

Figure A

12%

(13/110)

2

Figure B

7%

(8/110)

3

Figure C

7%

(8/110)

4

Figure D

7%

(8/110)

5

Figure E

64%

(70/110)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M1.HE.27) A 3-month-old African American infant presents to the hospital with 2 days of fever, "coke"-colored urine, and jaundice. The pregnancy was uneventful except the infant was found to have hyperbilirubinemia that was treated with phototherapy. The mother explains that she breastfeeds her child and recently was treated herself for a UTI with trimethoprim-sulfamethoxazole (TMP-SMX). Which of the following diseases is similarly inherited as the disease experienced by the child? Review Topic

QID: 107011
1

Marfan syndrome

15%

(4/27)

2

Sickle cell anemia

26%

(7/27)

3

Hemophilia A

41%

(11/27)

4

Beta thalassemia

7%

(2/27)

5

Rett syndrome

11%

(3/27)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.HE.86) A 32-year-old Greek male presents with a rash consistent with dermatitis herpetiformis and is treated with a course of oral dapsone. Over the following several days he becomes increasingly fatigued and experiences persistent back pain. Complete blood count reveals a normocytic anemia and urinalysis shows hemoglobinuria. Results from a peripheral blood smear are shown in Figure A. Which of the following is most likely responsible for this patient’s symptoms? Review Topic

QID: 101396
FIGURES:
1

Glucose-6-phosphate-dehydrogenase deficiency

82%

(73/89)

2

Pyruvate kinase deficiency

3%

(3/89)

3

Paroxysmal nocturnal hemoglobinuria

4%

(4/89)

4

Hereditary spherocytosis

8%

(7/89)

5

Cold immune hemolytic anemia

2%

(2/89)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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