Immunodeficiencies for Step 1: SCID, Bruton, CGD & More

Creator: Progress Note
Published: 2026-10-08
Keywords: immunodeficiency USMLE Step 1, immunodeficiency usmle, bruton agammaglobulinemia, digeorge syndrome catch 22, scid adenosine deaminase, chronic granulomatous disease catalase positive, leukocyte adhesion deficiency, wiskott aldrich syndrome, selective iga deficiency, complement deficiency neisseria

bolt The 60-second version

check_circleRecurrent encapsulated bacteria (sinusitis, pneumonia, otitis) → B-cell, complement, or splenic defect. Viral, fungal, and opportunistic infections → T-cell defect.
check_circleBruton X-linked agammaglobulinemia: BTK defect; absent B cells and all immunoglobulins; infections begin after about 6 months as maternal IgG fades.
check_circleDiGeorge syndrome: 22q11.2 deletion; thymic and parathyroid hypoplasia → T-cell deficiency and hypocalcemic tetany, plus conotruncal heart defects.
check_circleSCID: severe infections of every type in infancy, chronic diarrhea, thrush, failure to thrive, absent thymic shadow; most often X-linked IL-2 receptor γ-chain or adenosine deaminase deficiency.
check_circleChronic granulomatous disease: NADPH oxidase defect → infections with catalase-positive organisms (S. aureus, Aspergillus, Burkholderia, Serratia, Nocardia); abnormal dihydrorhodamine test.
check_circleTerminal complement (C5–C9) deficiency → recurrent Neisseria; C1 esterase inhibitor deficiency → hereditary angioedema.

target What you'll be able to do · aligned to USMLE Step 1 · Immunology

IMMUNOUse infection patterns to localize an immune defect.
IMMUNORecognize B-cell, T-cell, and combined immunodeficiencies with their genes and findings.
IMMUNODistinguish chronic granulomatous disease from leukocyte adhesion deficiency.
IMMUNOPredict the consequences of specific complement deficiencies.

How immunodeficiencies are tested on Step 1

Start with the infection pattern, then narrow to the specific defect.

Infection patterns. T-cell defects often produce combined problems because B cells need T-cell help.

B-cell and T-cell defects

Compare the most-tested syndromes.

Disorder	Defect	Key findings
Bruton XLA	BTK; X-linked recessive	Boys; absent B cells, all Ig ↓, small tonsils and lymph nodes
Selective IgA deficiency	Most common primary immunodeficiency	Often asymptomatic; sinopulmonary and GI infections; anaphylaxis to blood products containing IgA; associated with celiac disease
Common variable immunodeficiency	B-cell differentiation defect	Low immunoglobulins, often diagnosed in adolescence or adulthood; ↑ autoimmunity and lymphoma
DiGeorge syndrome	22q11.2 deletion	Absent thymic shadow, hypocalcemia, conotruncal heart defects, facial features
Hyper-IgE (Job) syndrome	STAT3; Th17 deficiency	Cold staphylococcal abscesses, retained primary teeth, eczema, high IgE, coarse facies

Memory aid for DiGeorge (CATCH-22): Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia, chromosome 22.

Combined immunodeficiencies

These affect both T- and B-cell function.

Combined defects. Avoid live vaccines in children with SCID or other significant T-cell defects.

Phagocyte and complement defects

Abscesses without pus or with catalase-positive organisms point to phagocytes.

Phagocyte defects. Chédiak-Higashi syndrome (LYST) adds giant granules in neutrophils, partial albinism, and neuropathy.

C1 esterase inhibitor deficiency: hereditary angioedema; swelling without hives; low C4; avoid ACE inhibitors.
C3 deficiency: severe recurrent pyogenic infections and immune complex disease.
C5–C9 deficiency: recurrent Neisseria infections.
Early classical pathway (C1–C4) deficiency: increased risk of SLE-like immune complex disease.

Worked example

Let the organism lead you.

functions Worked example — liver abscess in a boy

A 6-year-old boy has had recurrent skin abscesses and pneumonia, and now has a liver abscess growing Staphylococcus aureus. A prior pneumonia grew Aspergillus. Which test is most likely abnormal?

Recurrent infections with S. aureus and Aspergillus suggest a defect in killing catalase-positive organisms.
Catalase destroys the hydrogen peroxide these microbes make, so neutrophils must generate their own reactive oxygen species.
Defective NADPH oxidase prevents the respiratory burst: chronic granulomatous disease.
The dihydrorhodamine (DHR) flow cytometry test shows absent oxidative burst.

Answer. An abnormal dihydrorhodamine test from chronic granulomatous disease (NADPH oxidase deficiency).

Next in the roadmap

Immunodeficiencies

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quiz Test yourself

Quick check — 3 questions

1. An infant has hypocalcemic seizures, a heart defect, and no thymic shadow. Diagnosis?

2. Delayed umbilical cord separation and marked neutrophilia suggest:

3. A boy with eczema, recurrent infections, and bleeding with small platelets most likely has:

Frequently asked questions

Why do infections in Bruton agammaglobulinemia start after 6 months?expand_more

Maternal IgG transferred across the placenta protects the infant until it declines.

Which organisms infect patients with chronic granulomatous disease?expand_more

Catalase-positive organisms such as S. aureus, Aspergillus, Burkholderia cepacia, Serratia, and Nocardia.

What is the most common primary immunodeficiency?expand_more

Selective IgA deficiency, which is often asymptomatic.

Which complement deficiency causes recurrent Neisseria infections?expand_more

Deficiency of the terminal components C5–C9.

References & further reading

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