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
QUESTIONS 1 of 5 1 2 3 4 5 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI 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/LFemale: 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/mLFemale: 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/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative 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/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 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/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 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/minFemale: 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 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 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 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (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: A B C D E 1 Figure A 11% (13/121) 2 Figure B 7% (8/121) 3 Figure C 10% (12/121) 4 Figure D 7% (8/121) 5 Figure E 64% (77/121) 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 13% (4/30) 2 Sickle cell anemia 23% (7/30) 3 Hemophilia A 47% (14/30) 4 Beta thalassemia 7% (2/30) 5 Rett syndrome 10% (3/30) 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: A 1 Glucose-6-phosphate-dehydrogenase deficiency 83% (76/92) 2 Pyruvate kinase deficiency 3% (3/92) 3 Paroxysmal nocturnal hemoglobinuria 4% (4/92) 4 Hereditary spherocytosis 8% (7/92) 5 Cold immune hemolytic anemia 2% (2/92) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1