Snapshot A 6-year-old boy presents to the hospital with a severe upper respiratory infection requiring hospitalization. Chart review reveals that he has presented multiple times to the emergency room and primary care physician’s office for a variety of infections, including otitis media, upper respiratory infections, pneumonia, and sinusitis. When detailing family history, it is found that his maternal uncle died of an infection as a child. Lab findings include decreased levels of IgG, IgM, and IgA. Introduction Primary humoral immunodeficiency characterized by decreased immunoglobulins Genetics X-linked recessive seen in male children Pathogenesis defect in Bruton tyrosine kinase (BTK) defective maturation of B-cells impaired signaling from pre-B-cell receptor ↓ B-cells ↓ production of all classes of Ig impaired antibody immune response Presentation Symptoms recurrent infections especially after 6 months old (↓ maternal IgG) Streptococcus pneumoniae, Hemophilus influenzae, Streptoccocus pyogenes, and Pseudomonas increased susceptibility to encapsulated bacteria and blood-borne viruses due to opsonization defect Physical exam absent/scant lymphoid tissues (tonsils/lymph nodes) Evaluation Diagnosis based on family history, clinical history, and exam Serologies ↓ all classes of Ig ↓ levels of B-cells normal T-cells Diagnosis confirmed with DNA, mRNA, or protein analysis showing mutation in BTK Differential Diagnosis Common variable immunodeficiency Severe combined immunodeficiency Transient hypogammaglobulinemia of infancy Treatment Antibiotics for infections Regular IVIG infusions Prognosis, Prevention, and Complications Prognosis normal prognosis with regular IVIG therapy and early detection Prevention screening in newborns regular IVIG to prevent infections Complications small risk of malignancy
QUESTIONS 1 of 6 1 2 3 4 5 6 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 (M1.IM.1) Which of the following patient presentations seen in a pediatric immunology clinic is most consistent with a diagnosis of Bruton's agammaglobulinemia? Review Topic QID: 105399 1 A 15-month-old girl who has had repeated otitis media, pneumonia, and progressive clumsiness since beginning to walk in the past three months 5% (9/180) 2 A 10-month-old boy who has had recurrent viral infections as well as hypocalcemia during neonatal period 4% (7/180) 3 A 4-year-old girl who has had repeated oral candidasis in the past nine months 2% (4/180) 4 A 9-month-old boy who has had recurrent otitis media and pneumococcal pneumonia in the past three months 76% (137/180) 5 A 7-month-old boy who has had recurrent pneumococcal pneumonia, eczema, and easy bruising in the past four months 11% (20/180) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.74) A father brings his 9-month-old child into the pediatrician's office because he is concerned about his child's health. He states that starting a few months ago, the child has had recurrent infections, with the most recent being a Giardial infection. On physical exam, the child is well-appearing but the pediatrician notes an absence of tonsils. Concerned for a possible immunodeficiency, the pediatrician obtains Ig levels which demonstrates decreased IgM, IgG, IgA, and IgE. Which of the following pedigrees best represents the mode of inheritance of this patient's condition? Review Topic QID: 106663 FIGURES: A B C D E 1 Figure A 6% (8/134) 2 Figure B 8% (11/134) 3 Figure C 10% (14/134) 4 Figure D 60% (80/134) 5 Figure E 13% (18/134) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.IM.30) You are seeing a 4-year-old boy in clinic who is presenting with concern for a primary immune deficiency. He has an unremarkable birth history, but since the age of 6 months he has had recurrent otitis media, bacterial pneumonia, as well as two episodes of sinusitis, and four episodes of conjunctivitis. He has a maternal uncle who died from sepsis secondary to H. influenza pneumonia. If you drew blood work for diagnostic testing, which of the following would you expect to find? Review Topic QID: 105700 1 Abnormally low number of B cells 70% (30/43) 2 Abnormally low number of T cells 14% (6/43) 3 Abnormally high number of B cells 2% (1/43) 4 Abnormally high number of T cells 9% (4/43) 5 Elevated immunoglobulin levels 2% (1/43) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.IM.57) A 7-month-old Caucasian male presents with recurrent sinusitis and pharyngitis. The parents say that the child has had these symptoms multiple times in the past couple of months and a throat swab sample reveals the presence of Streptoccocus pneumoniae. Upon workup for immunodeficiency it is noted that serum levels of immunoglobulins are extremely low but T-cell levels are normal. Which of the following molecules is present on the cells that this patient lacks? Review Topic QID: 100478 1 CD4 20% (9/46) 2 CD8 9% (4/46) 3 CD3 7% (3/46) 4 CD19 54% (25/46) 5 NKG2D 2% (1/46) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4