Major Immunodeficiencies — Pediatric GI Comparison Chart (Responsive)

X‑linked Agammaglobulinemia (Bruton)

BTK mutation → arrest of B‑cell maturation; severe reduction/absence of mature B cells; pan‑hypogammaglobulinemia.

Infancy after maternal IgG wanes (≈6–12 months)

Recurrent bacterial sinopulmonary infections; failure to thrive in severe cases.

Chronic/recurrent GI infections (Giardia, Campylobacter); chronic diarrhea; malabsorption; rare enteroviral persistence.

Very low/absent CD19+/CD20+ B cells; markedly low IgG, IgA, IgM.

Regular IVIG/SCIG replacement; targeted antibiotics; avoid live vaccines until evaluated.

Consider Giardia in persistent diarrhea; evaluate vaccine responses; refer immunology early.

Chronic Granulomatous Disease (CGD)

NADPH oxidase complex defects (eg CYBB X‑linked or autosomal recessive genes) → impaired phagocyte respiratory burst and intracellular killing.

Early childhood; X‑linked forms are often more severe

Recurrent catalase‑positive bacterial and fungal infections; granulomatous inflammation and inflammatory complications.

Granulomatous colitis mimicking Crohn disease (strictures, fistulae); perianal disease; hepatic abscesses.

Abnormal nitroblue tetrazolium (NBT) or dihydrorhodamine (DHR) assay; elevated inflammatory markers during flares.

Prophylactic antibiotics/antifungals; IFN‑γ in selected patients; immunomodulation for GI inflammation; HSCT is curative option.

Differentiate from classic IBD; consider CGD testing in early/severe granulomatous colitis; HSCT for definitive therapy.

Common Variable Immunodeficiency (CVID)

Heterogeneous defects in B‑cell differentiation; often polygenic with occasional monogenic causes.

Late childhood, adolescence, or adulthood; pediatric presentations occur

Recurrent sinopulmonary infections; autoimmunity; lymphoproliferation; splenomegaly.

Chronic diarrhea from infections (Giardia); CVID enteropathy (villous atrophy, malabsorption); protein‑losing enteropathy; nodular lymphoid hyperplasia.

Low IgG with low IgA and/or IgM; poor vaccine responses; reduced switched memory B cells often present.

IVIG/SCIG replacement; treat infections aggressively; immunosuppression for enteropathy/autoimmunity when needed.

CVID enteropathy can mimic celiac disease but is seronegative; increased GI lymphoma risk—monitor long‑term.

HIV Infection / AIDS (pediatric)

Retroviral infection (mostly HIV‑1) causing progressive CD4+ T‑cell depletion and immune dysfunction.

Perinatal transmission → infancy; postnatal exposures possible

Recurrent/opportunistic infections, failure to thrive, lymphadenopathy; stage‑dependent manifestations.

Chronic diarrhea from opportunists (Cryptosporidium, CMV, MAC); oral/esophageal candidiasis; hepatosplenomegaly; malabsorption.

Low CD4 count (age‑adjusted); positive HIV RNA PCR; opportunistic infection diagnostics as indicated.

Antiretroviral therapy (ART); treat opportunistic GI infections; nutritional support.

Consider HIV testing in infants with chronic diarrhea and failure to thrive; prevention via maternal ART and post‑exposure prophylaxis.

Hyper IgM Syndrome

Defects in class‑switch recombination (eg CD40L X‑linked, AID, UNG) → inability to class switch from IgM to IgG/IgA.

Infancy / early childhood

Recurrent bacterial infections; opportunistic infections (Pneumocystis in X‑linked form); autoimmunity in some forms.

Severe diarrhea from enteric pathogens; cryptosporidial cholangitis causing prolonged diarrhea and biliary disease; malabsorption.

Elevated or normal IgM with low IgG and IgA; confirmatory genetic testing (eg CD40L mutation).

IVIG replacement; prophylactic antibiotics and Pneumocystis prophylaxis; HSCT curative for many genetic forms.

Cryptosporidium infection can cause sclerosing cholangitis—consider in chronic diarrhea with biliary disease; avoid live vaccines until evaluated.

Selective IgA Deficiency

Most common primary antibody deficiency; genetic basis heterogeneous and incompletely defined; selective absence of serum and secretory IgA.

Childhood or adolescence; many individuals asymptomatic

Recurrent sinopulmonary infections, allergic disease, and autoimmunity in some patients.

Increased susceptibility to GI infections (Giardia); association with celiac disease and autoimmune enteropathy reported.

Low/undetectable serum IgA with normal IgG and IgM; vaccine responses typically intact.

Supportive care and treat infections; no routine Ig replacement; use IgA‑deficient blood products caution if anti‑IgA present.

Many are asymptomatic; screen for celiac disease when GI symptoms present; watch for transfusion reactions in anti‑IgA patients.

IL‑10 / IL‑10 Receptor Deficiency

Autosomal recessive defects in IL10, IL10RA, or IL10RB → loss of anti‑inflammatory signaling and uncontrolled intestinal inflammation.

Neonatal period to early infancy (very early onset IBD)

Severe, treatment‑refractory colitis with perianal disease and fistulae; failure to thrive and systemic inflammation.

Diffuse colitis with early‑onset IBD phenotype; severe perianal disease, strictures, and high risk of colorectal complications.

Elevated inflammatory markers; diagnosis by genetic testing; biopsy shows deep ulceration and dense inflammatory infiltrate.

HSCT is definitive/curative; medical therapy often insufficient and used as bridge to transplant.

Consider in infants with very‑early onset, treatment‑refractory IBD; early genetic testing expedites transplant referral.

Severe Combined Immunodeficiency (SCID)

Group of genetic defects (eg IL2RG X‑linked, RAG1/2, ADA) → profound defects in T‑cell development ± B/NK cells; absent adaptive immunity.

Infancy; usually presents in first months of life

Recurrent severe infections (viral, fungal, opportunistic), thrush, failure to thrive, chronic diarrhea.

Chronic severe diarrhea from enteric viruses and protozoa; persistent mucosal infections and enteropathy.

Low/absent T cells; poor lymphocyte proliferation to mitogens; low immunoglobulins (maternal IgG may transiently mask).

Protective isolation, prophylactic antimicrobials, IVIG; definitive HSCT, enzyme replacement (ADA), or gene therapy where available.

Newborn TREC screening identifies many cases early—urgent HSCT referral; avoid live vaccines and exposures until treated.

Wiskott‑Aldrich Syndrome (WAS)

X‑linked WAS gene mutation → defective cytoskeletal regulation in hematopoietic cells; combined immunodeficiency with thrombocytopenia and eczema.

Infancy to early childhood

Recurrent infections, eczema, microthrombocytopenia; later autoimmunity and malignancy risk.

Recurrent GI bleeding due to thrombocytopenia; mucosal infections (CMV, Giardia) causing diarrhea; colitis and protein‑losing enteropathy reported.

Thrombocytopenia with small platelets; variable Ig abnormalities (low IgM, elevated IgA/IgE possible); abnormal T‑cell function.

Supportive care, platelet transfusions for bleeding, IVIG for infections; HSCT is curative; gene therapy in selected centers.

Suspect WAS with the triad of bleeding + eczema + recurrent infections; coordinate hematology and immunology early.

Major Immunodeficiencies seen in Pediatric GI

(Comparison Chart)