Lecture 2: Non-Neoplastic WBC Disorders in Pediatrics Flashcards
How to calculated absolute neutrophil count (ANC)?
ANC = [(% neutrophils + %bands) x (WBC)] / 100
If the absolute neutrophil count (ANC) is
ANC <500/uL
What is the inheritance pattern, clinical manifestations and the defect in Kostmann Syndrome?
- Autosomal recessive
- ANC <200 since birth; manifests as life-threatening pyogenic infections, often in infancy
- Due to impaire myeloid differentiation caused by maturational arrest of neutrophil precursors
Severe congenital neutropenia (Kostmann syndrome) increases the risk for what?
Leukemia (AML)
What are the clinical manifestations and defect associated with Cyclic neutropenia?
- Cyclic fever, oral ulcers, gingivitis, periodontal disease, and recurrent bacterial infections
- ANC <200 for 3-7 days every 3 weeks
- Due to stem cell regulatory defect resulting in defective maturation
What is the inheritance pattern and risk for malignancy associated with Cyclic neutropenia?
- Can be sporadic or autosomal dominant
- NO increased risk malignancy
What is the triad associated with Shwachman-Diamond syndrome?
- Neutropenia
- Exocrine pancreas insufficiency = loose oily stools
- Skeletal abnormalities
What is the inheritance pattern and defect seen with Shwachman-Diamond syndrome?
- Autosomal recessive
- Defect in neutrophil mobility, migration,andchemotaxisin addition toneutropenia
Shwachman-Diamond syndrome is associated with an increased risk for what?
Myelodysplastic syndrome or leukemia
Fanconi anemia is the classic example of which triad?
- Pancytopenia
- Bone marrow failure
- Aplastic anemia
What are the clinical manifestations of leukocyte adhesion deficiency?
- Delayed separation of umbilical cord (>3 weeks)
- Recurrent severe bacterial and fungal infections WITHOUT pus
- Poor wound healing
- Periodontal disease
What is the triad of hyper-IgE aka Job syndrome?
- Severe eczema
- Recurrent bacterial infections (usually staph) of skin
- Recurrent pulmonary infections (bacterial, fungal)
What is the defect in Hyper-IgE aka Job syndrome; increased risk of what malignancy?
- Defect in chemotaxis of neutrophils
- ↑ risk of Hodgkin lymphoma
What are the 4 main clinical manifestations of Chediak-Higashi syndrome; what is the inheritance pattern?
- Autosomal recessive; defect in granule morphogenesis, chemotaxis, and degranulation
- Partial oculocutaneous ALBINISM
- Peripheral and cranial neuropathies
- Neutropenia
- Recurrent pyogenic infections
What are the clinical manifestations of Chronic Granulomatous disease; what is the inheritance pattern?
- Primarily X-linked recessive
- Recurrent purulent infections w/ fungal or bacterial catalase-positive organisms
- Usually begins in infancy, chronic inflammatory granulomas
What is infection associated neutropenia; common viruses?
- Many viruses cause neutropenia within first 2-3 days of illness, lasting up to 1 weeks
- Common: HIV, Parvovirus B19, EBV, CMV, Influenza A and B, RSV
Which nutritional deficiencies are associated with neutropenia?
- Vitamin B12
- Folate
- Copper
- Starvation
Seizures are a cause of what WBC abnormality?
Leukocytosis
How is severe congenital neutropenia (Kostmann syndrome) diagnosed; which mutation may be present?
BM demonstrates myeloid maturation arrest; 60-80% have neutrophil ELA-2 mutations
How is Cyclic Neutropenia diagnosed; which mutation may be present?
CBC 2-3x weekly for 6-8 weeks to document cycles and nadir; ELA-2 mutation in 80-90%
What is seen on evaluation and what findings aid in diagnosis of Shwachman-Diamond syndrome; which mutation may be present?
- Neutropenia
- Low serum trypsinogen + ↑ fecal fat excretion (exocrine pancreas insufficiency)
- Metaphyseal dysostosis, rib cage abnormalities, short stature
- SBDS mutation in 90%
What is th inheritance pattern of Leukocyte Adhesion Deficiency?
Autosomal Recessive
Which class of drugs is notorious for causing neutropenia?
Cytotoxic agents for tx of malignancies
