heme-onc truelearn Q's

severe combined immunodeficiency (SCID)

combined T & B cell disorder

Most common: X-linked IL-2 receptor γ-chain mutation

• → defective cytokine signaling

• → abnormal lymphocyte development.

Other classic cause: Adenosine deaminase (ADA) deficiency

• → ↑ toxic purine metabolites

• → lymphocyte destruction.

severe combined immunodeficiency (SCID)

Newborn screen: ↓ TRECs (T-cell receptor excision circles)

severe combined immunodeficiency (SCID)

_{⭐ Infant with recurrent severe bacterial, viral, fungal, AND protozoal infections
⭐ Chronic diarrhea + failure to thrive
⭐ Oral thrush (Candida)
⭐ Infections begin after maternal antibodies wear off}

_{DO NOT GIVE LIVE VACCINES}

Baby + recurrent infections of ALL types + thrush + chronic diarrhea + failure to thrive + absent thymic shadow

Abx prophylaxis & IVIG

Hematopoietic stem-cell transplant is definitive.

rx of SCID

Bruton X-Linked Agammaglobulinemia (XLA)

_{X-linked mutation in BTK (Bruton tyrosine kinase)
→ B cells cannot mature past the pre-B-cell stage}

Failure of B-cell maturation → essentially no mature B cells → ↓ all immunoglobulins.

Bruton X-Linked Agammaglobulinemia (XLA)

_{X-linked mutation in BTK (Bruton tyrosine kinase)
→ B cells cannot mature past the pre-B-cell stage}

onset ~6mo’s after maternal IgG declines

Recurrent sinopulmonary bacterial/encapsulated infections

incr risk of giardia infx

avoid live vaccines
Absent/small tonsils and lymph nodes
↓ B cells + ↓ all immunoglobulins

tx: IVIG

Common Variable Immunodeficiency (CVID)

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	Bruton XLA	CVID
B cells	❌ Absent	✅ Present
Immunoglobulins	↓↓↓	↓
Typical onset	~6 months, boys	Later
Defect	BTK → can't make mature B cells	B cells can't become effective plasma cells
Treatment	IVIG	IVIG

Definition: B cells are present but don't differentiate properly into plasma cells → ↓ antibody production.

Feature
B cells	Normal/present
Plasma cells	↓
IgG	↓
IgA / IgM	Often ↓
T cells	Usually normal
Presentation	Later — childhood, adolescence, or adulthood
Infections	Recurrent sinopulmonary infections, especially encapsulated bacteria
Other associations	Autoimmune disease, GI infections/Giardia, ↑ lymphoma risk
Treatment	IVIG/SCIG

Common Variable Immunodeficiency (CVID)

Older child/adult + recurrent sinus/pulmonary infections + low immunoglobulins BUT normal B-cell count →

Diamond-Blackfan Anemia (DBA)

(AD)

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—NO ERYTHROBLASTS ON BM

Feature	Diamond-Blackfan
Problem	↓ RBC production
Cause	Ribosomal protein mutation
Inheritance	Often autosomal dominant
Hemoglobin	↓
MCV	↑ (macrocytic)
Reticulocytes	↓↓
WBCs / platelets	Usually normal
Bone marrow	↓/absent erythroid precursors
HbF	↑
Erythrocyte ADA	↑
Physical findings	Craniofacial abnormalities, thumb/upper-limb defects, short stature
Cancer risk	↑ MDS/AML and solid tumors

Congenital pure red blood cell aplasia → bone marrow fails to produce RBCs, while WBCs and platelets are generally normal.

• infant <1 year + severe macrocytic anemia + congenital abnormalities

Treatment:

• Corticosteroids → first-line

• Chronic RBC transfusions if needed

• Stem-cell transplant → potentially curative

Diamond-Blackfan Anemia (DBA)

Baby + macrocytic anemia + very low reticulocytes + normal WBC/platelets + thumb/craniofacial abnormalities + mimics turners: shielded chest, webbed neck

Fanconi Anemia

Feature	Fanconi anemia
Inheritance	Usually autosomal recessive
Defect	DNA interstrand cross-link repair
RBCs	↓
WBCs	↓
Platelets	↓ → pancytopenia
MCV	↑ macrocytic
Reticulocytes	↓
Physical findings	Thumb/radial abnormalities, short stature, microcephaly, café-au-lait/hyperpigmentation
Cancer risk	↑ AML/MDS and solid tumors
Definitive treatment	Hematopoietic stem-cell transplant

Inherited DNA repair defect → progressive bone marrow failure → pancytopenia.

Child + pancytopenia + short stature + abnormal thumbs/radii + café-au-lait spots

Wiskott-Aldrich Syndrome (WAS)

• W = Wiskott

• E = Eczema

• T = Thrombocytopenia

X-linked (boys») immunodeficiency caused by a WAS gene mutation → abnormal actin cytoskeleton → impaired immune-cell function.

• increase in IgA, IgE

• decrease in IgM

• normal/decrease IgG

recurrent bacteria/viral infx

incr risk of lymphoma/leaukemia

Wiskott-Aldrich Syndrome (WAS)

Young boy + eczema + recurrent infections + bleeding/petechiae + LOW, SMALL platelets →

Hyper-IgE Syndrome (Job Syndrome)

Immunodeficiency caused by impaired Th17 cell development → ↓ neutrophil recruitment to sites of infection.

Classic mutation	STAT3
Th17 cells	↓
IgE	↑↑↑
Eosinophils	↑
Eczema	✅
Infections	Recurrent Staph aureus
Abscesses	“Cold” → little inflammation
Lungs	Recurrent pneumonia → pneumatoceles
Teeth	Retained primary (baby) teeth
Skeletal	Fractures, scoliosis
Face	Coarse facial features

Hyper-IgE Syndrome (Job Syndrome)

“Cold” staph abscesses + eczema + very high IgE + retained primary teeth

Chediak-Higashi Syndrome

• ^{C = Can't form phagolysosomes}

• ^{H = Hypopigmentation}

• ^{S = Staph/Strep infections}

Autosomal recessive LYST gene defect → impaired lysosomal trafficking/phagolysosome formation → defective killing by neutrophils.

Feature
Gene	LYST
Inheritance	Autosomal recessive
Main defect	↓ Phagolysosome formation
Infections	Recurrent Staph & Strep infections
Skin/hair	Partial albinism / silvery hair
Neuro	Peripheral neuropathy
Blood smear	⭐ Giant granules in granulocytes
Bleeding	Can occur from platelet dysfunction
Treatment	Hematopoietic stem-cell transplant

Chediak-Higashi Syndrome

Child with recurrent infections + albinism + neuropathy + giant granules in neutrophils →