Updated: 4/6/2017

Wiskott-Aldrich Syndrome

Topic
Review Topic
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Questions
5
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Evidence
4
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Snapshot
  • An 8-year-old boy is brought to his pediatrician for easy bruising. On physical exam, he is found with petechiae and purpura in multiple areas over his body, as well as bruises over his arms. Eczematous patches are also found on his flexural surfaces. Laboratory results reveal thrombocytopenia to 30,000/mm3. Further questioning reveals a past medical history of multiple hospital stays due to pneumonia and otitis media infections as well as recurrent epistaxis.
Introduction
  • Primary immunodeficiency disorder of B and T cells
  • Pathogenesis
    • mutation in WAS gene encoding Wiskott-Aldrich syndrome protein (WASp)
      • impaired actin cytoskeleton
      • results in defective T cell signalling and interactions with APCs
      • also impairs phagocytosis and chemotaxis
    • loss of cellular and humoral response
  • Genetics
    • X-linked recessive
  • To remember (WATER)
    • Wiskott
    • Aldrich
    • Thrombocytopenic purpura
    • Eczema
    • Recurrent infections
Presentation
  • Symptoms/physical exam
    • recurrent bacterial, viral, fungal infections
      • frequency increases with age
      • bacterial agents: Streptococcus pneumonia, Haemophilus influenza, Neisseria meningitides
      • viral agents: varicella and CMV
      • fungal infections: Candida albicans
    • thrombocytopenia
      • recurrent bleeding, especially in first days of life
        • petechiae
        • purpura
        • easy bruising
        • hematemesis
        • epistaxis
        • hematuria
    • chronic eczema
    • hepatosplenomegaly common
Evaluation
  • Serologies
    • ↓ number of T and B cells
    • ↓ to normal IgG, IgM
    • ↑ IgE, IgA
  • Labs
    • thrombocytopenia
      • usually 20,000/mm3 - 50,000/mm3
  • Gene sequence analysis of WAS essential to confirm diagnosis
Differential Diagnosis
  • Severe combined immunodeficiency
  • Hyper IgE syndrome (also with eczema)
  • Atopic dermatitis
Treatment
  • Antibiotics
  • IVIG
  • Hematopoietic stem cell transplantation
    • only curative treatment
Prognosis, Prevention, and Complications
  • Prognosis
    • reduced life expectancy (see complications below)
    • bleeding is main cause of death
  • Complications
    • increased risk of
      • autoimmune diseases
      • malignancies (lymphomas, leukemias), usually fatal
      • infections
    • complications may lead to early death
    • chronic eczema
      • superinfection
 

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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.IM.4707) A 2-year-old boy is brought to his pediatrician for evaluation of high fever and malaise. His mother relates that he suffers from frequent infections and has had several episodes of bloody diarrhea in the last year. Physical exam reveals diffuse petechial lesions as well as dry red skin in the elbow and other extremity flexor compartments. His mom remembers that one of her nephews has a similar problem with bleeding and very itchy rashes but cannot recall the details. Which of the following patterns of immunoglobulin findings is most likely to be found in this patient (see Figure A)? Review Topic

QID: 108432
FIGURES:
1

A

14%

(36/256)

2

B

20%

(51/256)

3

C

15%

(38/256)

4

D

29%

(75/256)

5

E

16%

(42/256)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M1.IM.74) A 2-month-old boy is brought to his pediatrician for a routine visit. His mother is concerned because he developed a rash one month ago that has not resolved (Figure A). Furthermore, she states that he has seemed to constantly be sick ever since his birth. On physical exam, the pediatrician notes the findings demonstrated in Figure B. The pediatrician pursues further workup and orders a number of lab tests. Which of the following laboratory findings is most likely to be observed in this patient? Review Topic

QID: 106655
FIGURES:
1

Increased IgM; Decreased IgG, IgA, IgE

22%

(29/132)

2

Increased IgE only

7%

(9/132)

3

Increased IgE, IgA; Decreased IgM

33%

(44/132)

4

Increased IgE; Decreased IgG, IgM

21%

(28/132)

5

Decreased IgE, IgM, IgA, IgG

15%

(20/132)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.IM.63) A 3-year-old boy is brought to the family physician by his parents. They are concerned that he has had multiple nosebleeds in the last 6 months and is always sick compared to other children. During this time period they have also noticed the formation of multiple bruises on his extremities and dry-itching skin on his hands, feet and elbow. On physical exam the physician notes moderate splenomegaly. What is the most likely diagnosis in this child? Review Topic

QID: 105461
1

X-linked Agammaglobulinemia

14%

(6/42)

2

Severe Combined Immunodefiency

10%

(4/42)

3

Wiskott-Aldrich Syndrome

71%

(30/42)

4

Primary Eczema

0%

(0/42)

5

Hyperimmunoglobulin E syndrome

2%

(1/42)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.IM.43) A 7-year-old boy presents to your office with facial eczema. He has a history of multiple, recurrent infections, including multiple episodes of pneumonia that lasted several weeks and otitis media. Laboratory measurements of serum immunoglobulins showed increased IgE and IgA but decreased IgM. Which of the following additional abonormalities would you expect to observe in this patient? Review Topic

QID: 100464
1

Thrombocytopenia

49%

(23/47)

2

Leukopenia

17%

(8/47)

3

Anemia

9%

(4/47)

4

Pancreatic insufficiency

2%

(1/47)

5

NADPH oxidase deficiency

17%

(8/47)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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