Major Immunodeficiencies seen in Pediatric GI

(Alternative Comparison Chart)

Immunodeficiency	Genetics / Pathogenesis	Typical onset	Clinical features	GI findings	Key lab findings	Treatment	Clinical pearls
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) Malabsorption, chronic diarrhea; rare enteroviral persistence	Very low/absent CD19+/CD20+ B cells Markedly low IgG, IgA, IgM	Regular IVIG/SCIG replacement Targeted antibiotics; prophylaxis when indicated Avoid live vaccines until evaluated	Consider Giardia with persistent diarrhea despite normal workup Assess vaccine responses; refer immunology early
Chronic Granulomatous Disease (CGD)	NADPH oxidase complex defects (eg CYBB X‑linked or autosomal genes) Impaired phagocyte respiratory burst → defective intracellular killing	Early childhood; X‑linked 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; granulomas throughout GI tract	Abnormal nitroblue tetrazolium (NBT) or dihydrorhodamine (DHR) test Elevated inflammatory markers during flares	Prophylactic antibiotics and antifungals; IFN‑γ for select patients Immunomodulation for inflammatory GI disease (steroids, azathioprine, biologics with caution) HSCT is curative option	Differentiate from classic IBD; test for CGD in early/severe granulomatous colitis HSCT for definitive therapy
Common Variable Immunodeficiency (CVID)	Heterogeneous defects in B‑cell differentiation; often polygenic Some monogenic causes identified	Late childhood, adolescence, or adulthood; pediatric cases 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	IVIG/SCIG replacement Treat infections aggressively Immunosuppression for enteropathy/autoimmunity when needed	CVID enteropathy can mimic celiac disease but is seronegative Monitor for GI lymphoma risk
HIV Infection / AIDS (pediatric)	Retroviral infection (HIV‑1) causing progressive CD4+ T‑cell depletion Immune dysfunction with opportunistic infection risk	Perinatal transmission → infancy; postnatal exposures possible	Recurrent/opportunistic infections, failure to thrive, lymphadenopathy Systemic manifestations depend on stage and ART status	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) Treatment of opportunistic GI infections; nutritional support	Consider HIV testing in infants with chronic diarrhea and failure to thrive Maternal ART and prophylaxis are critical for prevention
Hyper IgM Syndrome	Defects in class‑switch recombination (eg CD40L X‑linked, AID, UNG) Failure to produce IgG/IgA from IgM	Infancy / early childhood	Recurrent bacterial infections; opportunistic infections (Pneumocystis in X‑linked form) Autoimmunity and lymphoproliferation in some forms	Severe diarrhea from enteric pathogens Cryptosporidial cholangitis with prolonged diarrhea and biliary disease Malabsorption and failure to thrive	Elevated/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 can cause sclerosing cholangitis—consider with chronic diarrhea and biliary disease Avoid live vaccines until immunodeficiency evaluated
Selective IgA Deficiency	Most common primary antibody deficiency; genetic basis heterogeneous Selective absence of serum and secretory IgA	Childhood or adolescence; many are asymptomatic	Recurrent sinopulmonary infections, allergic disease, autoimmunity in some patients	Increased susceptibility to giardiasis and recurrent GI infections Association with celiac disease and autoimmune enteropathy reported	Low/undetectable serum IgA with normal IgG and IgM Vaccine responses typically preserved	Supportive care and treat infections No routine Ig replacement; caution with blood products if anti‑IgA antibodies present	Many are asymptomatic; screen for celiac disease when GI symptoms present Beware anaphylactic transfusion reactions in anti‑IgA alloimmunized patients
IL‑10 / IL‑10 Receptor Deficiency	Autosomal recessive defects in IL10, IL10RA, IL10RB Loss of anti‑inflammatory signaling leading to uncontrolled intestinal inflammation	Neonatal period to early infancy (very early onset IBD)	Severe, treatment‑refractory colitis; perianal disease and fistulae Failure to thrive and systemic inflammation	Diffuse colitis with early‑onset IBD phenotype; severe perianal disease High risk of early colorectal complications and strictures	Elevated inflammatory markers; genetic testing confirms diagnosis Histology: deep ulceration and dense inflammatory infiltrate	HSCT is definitive/curative Medical therapy often insufficient; used as bridge to transplant	Consider in infants with very‑early onset, treatment‑refractory IBD Early genetic testing expedites HSCT referral
Severe Combined Immunodeficiency (SCID)	Genetic defects (eg IL2RG X‑linked, RAG1/2, ADA) → defective T‑cell development ± B/NK defects Profound combined immunodeficiency	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/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 when available	Newborn TREC screening identifies many cases early—urgent HSCT referral Avoid live vaccines and infectious 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 from thrombocytopenia; mucosal infections causing diarrhea (CMV, Giardia) 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 bleeding + eczema + recurrent infections Coordinate hematology and immunology early for GI bleeding and immune care

Notes: This chart summarizes major immunodeficiencies relevant to pediatric gastroenterology. Individual presentations vary; consult immunology for definitive diagnosis, genetic testing, and management decisions. Live vaccines should be avoided until immunodeficiency has been excluded. For infants with chronic diarrhea, failure to thrive, unusual infections, or refractory inflammatory bowel disease, consider early immunologic evaluation.