Snapshot A 2-month-old baby boy is brought in for an urgent visit to the pediatrician. He has had several ear infections in his short lifetime and now seems to be struggling with a cold. On physical exam, his tongue is noted to be coated with white film. His scalp and face are covered with a flaky dandruff-like substance. Immediately concerned, his pediatrician orders a chest radiograph, which shows absence of thymic shadow. Flow cytometry is ordered. Introduction Combined B- and T-cell disorder causing immunodeficiency Life-threatening disease of recurrent infections Pathogenesis multiple variants found most common is X-linked defective common gamma chain found in IL-2R, IL-4R, and IL-7R defective T-cell activation autosomal recessive adenosine deaminase deficiency 2nd most common ↑ deoxyadenosine, which is toxic to lymphocytes ↓ DNA synthesis autosomal recessive JAK3 deficiency B-cells decreased immunoglobulin production T-cells markedly decreased T-cells Presentation Symptoms symptoms present < 3 months of age failure to thrive recurrent bacterial, viral, fungal, and protozoal infections chronic diarrhea Physical exam may see thrush in mouth and diaper area eczematous dermatitis erythroderma (> 90% body surface area involvement) severe seborrheic dermatitis diffuse alopecia absent lymphatic tissue, including tonsils and thymus Evaluation Diagnosis often delayed due to maternal IgG protecting baby in first few months of life ↓ Lymphocyte count (< 3000/μL) Chest radiography with no thymic shadow Flow cytometry absent T-cells abnormal function of B-cells Differential Diagnosis Hypogammaglobulinemia DiGeorge syndrome Hyper-IgM syndrome Ataxia-telangiectasia Treatment Bone marrow transplant life-saving treatment no concerns for allograft rejection Gene therapy Prognosis, Prevention, and Complications Prognosis without intervention, death by 2 years patients < 6 months of age who receive transplant have the best outcomes Complications severe infection death
QUESTIONS 1 of 7 1 2 3 4 5 6 7 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.39) A 3-year-old Cuban-American male has a history of recurrent Pseudomonas and Candida infections. Laboratory analysis reveals no electrolyte abnormalities. Examination of his serum shows decreased levels of IgG and CT scan reveals the absence of a thymus. The child likely has: Review Topic QID: 100460 1 Severe combined immunodeficiency syndrome 55% (22/40) 2 X-linked agammaglobinemia 5% (2/40) 3 DiGeorge syndrome 35% (14/40) 4 Isolated IgA deficiency 0% (0/40) 5 Common variable immunodeficiency 0% (0/40) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.IM.40) A 2-year-old Caucasian male presents with recurrent diaper rash and oral thrush. He has also experienced recurrent episodes of otitis media from repeat Streptoccous pneumoniae. He notably has reduced T and B cell counts. What disease is the child suffering from? Review Topic QID: 100461 1 X-linked agammaglobulinemia 23% (53/227) 2 Isolated IgA deficiency 9% (20/227) 3 Severe combined immunodeficiency 53% (121/227) 4 DiGeorge syndrome 9% (20/227) 5 MHC class II deficiency 2% (5/227) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.IM.5) A 6-year-old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases? Review Topic QID: 100426 1 DiGeorge Syndrome 6% (3/54) 2 Severe Combined Immunodeficiency 72% (39/54) 3 Hyper-IgM Syndrome 0% (0/54) 4 Wiskott-Aldrich Syndrome 7% (4/54) 5 Bruton's Agammaglobulinemia 13% (7/54) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 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.IM.74) A 4-month-old boy is brought to the pediatrician by his foster mother. She has no knowledge of his birth history but states that, for the past 3 months, he has had multiple viral and bacterial infections in addition to repeated bouts of diarrhea. On exam, the pediatrician observes the findings demonstrated in Figure A. The pediatrician tells the foster mother he is concerned the child may have an immunodeficiency. Levels of which of the following would be most likely to be reduced in this patient? Review Topic QID: 106688 FIGURES: A 1 Inosine 36% (62/171) 2 Adenosine 39% (66/171) 3 Cytosine 5% (9/171) 4 Thymine 15% (25/171) 5 Uracil 4% (7/171) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1