White cells

Question 1

Chronic granulomatous disease:

• Most common mutation
• Underlying pathophysiology

Answer 1

• gp91phox (XL)

- Defects in phagocyte NADPH oxidase complex

Question 2

Chronic granulomatous disease

- Clinical presentation

Answer 2

• Recurrent infx in skin, lung and LN in infancy
• Osteomyelitis, liver abcesses
• Chronic inflammatory granulomas

Question 3

Chronic granulomatous disease

- 5 typical micro-organisms

Answer 3

S. aureus
Burkholderia cepacia
Serratia marscescens
Aspergillus
Nocardia

Question 4

Chronic granulomatous disease

Treatment

Answer 4

Prophylaxis with sulfa and itraconazole
Prophylactic IFN-gamma (3 times/week)
BMT

Question 5

A young boy presents with episodic neutropenia, cardiomyopathy and methylglutaconic aciduria.
What is the diagnosis?
Which gene mutation is associated?

Answer 5

Barth syndrome

TAZ1

Question 6

What does the acronym WHIM stands for?

Answer 6

Warts
Hypogammaglobulinemia
Infection
Myelokathexis

Question 7

Name 5 drugs (outside chemotherapy) associated with neutropenia

Answer 7

• Penicillin
• Cephalosporin
• Phenothiazine
• Phenytoin
• Phenobarbital

Question 8

What is the definition of eosinophilia?

Answer 8

Eosinophil > 500

Question 9

What is the inheritance of Pearson syndrome?

What are the associated findings?

Answer 9

Mitochondrial

Neutropenia leading to pancytopenia, ringed sideroblasts
with multi-organ dysfunction

Question 10

A 4 y.o. girl presents with hepatomegaly, growth retardation and recurrent infection. Investigation reveal neutrophil dysfunction.

What is the diagnosis?
Bonus: associated mutation

Answer 10

Glycogen storage disease type I

Gene: G6PT1 (AR)

Question 11

What is the lenght of cycles in cyclic neutropenia?

Answer 11

21 +/- 3 days

Question 12

Chediak-Higashi synd: main characteristic features

Answer 12

• Partial albinism
• Changes in skin and hair
• Retinal changes (photophobia)
• Neutropenia
• Giant granules in leukocytes

Question 13

What diseases (2) are associated with mutation in ELANE, the elastase gene?

Answer 13

• Cyclic neutropenia

- Severe congenital neutropenia (AD)

Question 14

Mycobacterial infections and listeria meningitis: what defects to keep in mind?

Answer 14

Defects of INF-gamma + IL-12 axis

Question 15

What is the phenotype of Hyper-IgE syndrome?

Answer 15

• Eczema
• Staphylococcal skin infections
• Pneumonias
• Skeletal problems: delayed tooth eruption, scoliosis, etc.

Question 16

What genes are related to Hyper-IgE syndrome?

Answer 16

STAT3, DOCK8

Question 17

Neonatal alloimmune neutropenia:

• Causes
• Duration

Answer 17

• Maternal IgG directed against neutrophils Ag (often HNA1, HNA2) leading to destruction of neonatal neutrophils
• Up to 6 months

Question 18

What is the classical presentation of MPO deficiency?

Answer 18

• Recurrent fungal infections

- Diabetes

Question 19

What is the classical presentation of LAD?

Answer 19

• Delayed umbilical cord separation
• Recurrent bacterial infections (skin and mouth)
• Absent pus formation (no neutrophils in wound biopsy)
• Impaired wound healing
• Leukocytosis

Question 20

What abnormality is found in LAD?

Answer 20

Absence of CD11, CD18

Question 21

What is the classical presentation of specific granules deficiency?

Answer 21

– Decreased chemotaxis and microbicidal activity
– Mild neutropenia with bi-lobed neutrophils
– Recurrent skin and deep tissue infections (S. aureus, Gram-negative bacteria, Pseudomonas aeruginosa, Candida albicans)

Question 22

What abnormality is found in specific granule deficiency?

Answer 22

CEBP e

Question 23

Name 4 genes associated with dyskeratosis congenita?

Answer 23

1. DKC1
2. ACD
3. CTC1
4. NOP10