Overview X-linked agammaglobulinaemia (XLA) is a rare primary immunodeficiency caused by mutations in the Bruton’s tyrosine kinase (BTK) gene, leading to failure of B-cell maturation. It results in profound hypogammaglobulinaemia and susceptibility to recurrent bacterial infections, particularly with encapsulated organisms. It usually presents after 6 months of age (once maternal IgG wanes). Prevalence is ~1 […]

Overview Wiskott–Aldrich syndrome is a rare X-linked recessive primary immunodeficiency caused by mutations in the WAS gene, leading to defective actin cytoskeleton regulation in hematopoietic cells. It presents with the triad of eczema, recurrent infections, and thrombocytopenia with small platelets. Patients are prone to autoimmunity and malignancy. Incidence is ~1 in 100,000 live male births. […]

Overview Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency, characterised by profound defects in both humoral (B-cell) and cellular (T-cell) immunity. It presents in infancy with recurrent, severe, and opportunistic infections, chronic diarrhoea, and failure to thrive. Without curative therapy, most infants die within the first year of life. Incidence is […]

Overview Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency characterised by recurrent bacterial and fungal infections, impaired wound healing, and absence of pus formation due to defective leukocyte adhesion and migration. It results from genetic defects in leukocyte integrins or signalling pathways, preventing neutrophil extravasation from blood vessels into tissues. LAD has an estimated […]

Overview Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterised by markedly elevated serum IgE, recurrent staphylococcal skin and lung infections, eczema, and connective tissue/ skeletal abnormalities. Most commonly caused by autosomal dominant mutations in STAT3, it results in impaired Th17 cell differentiation and defective neutrophil chemotaxis. Autosomal recessive forms (DOCK8, TYK2 mutations) present with […]

Overview DiGeorge syndrome (22q11.2 deletion syndrome) is a congenital immunodeficiency and multisystem disorder caused by a microdeletion on chromosome 22. It leads to defective development of the third and fourth pharyngeal pouches, resulting in thymic hypoplasia/aplasia, hypocalcaemia due to parathyroid hypoplasia, and congenital heart defects. Prevalence is estimated at 1 in 4000 live births. Clinical […]

Overview Complement deficiencies are rare primary immunodeficiencies resulting from inherited absence or dysfunction of complement proteins, regulators, or receptors. They predispose to recurrent bacterial infections, autoimmune disease (particularly systemic lupus erythematosus–like syndromes), and in some cases angioedema. Complement proteins play a central role in innate immunity by opsonisation, chemotaxis, and direct lysis of pathogens via […]

Overview Common Variable Immunodeficiency (CVID) is the most frequent clinically significant primary antibody deficiency, characterised by hypogammaglobulinaemia and impaired antibody responses. It typically presents with recurrent bacterial infections, autoimmunity, granulomatous disease, and an increased risk of malignancy. CVID affects both sexes equally, with a prevalence of ~1 in 25,000–50,000 individuals. Diagnosis is often delayed, with […]

Overview Chronic granulomatous disease (CGD) is a rare, inherited primary immunodeficiency characterised by defective function of the NADPH oxidase enzyme complex in phagocytes, leading to failure of the oxidative burst required for intracellular killing of pathogens. This results in recurrent, often life-threatening bacterial and fungal infections, particularly with catalase-positive organisms, and predisposes to granuloma formation […]

Overview Hypermobility Spectrum Disorder (HSD) describes symptomatic joint hypermobility with musculoskeletal (and sometimes systemic) consequences in people who do not meet the 2017 diagnostic criteria for hypermobile Ehlers–Danlos syndrome (hEDS) or another heritable connective-tissue disorder (HCTD). Prevalence of generalised joint hypermobility varies (≈2–35% depending on age/sex/ethnicity and cut-offs), with symptomatic states more common in females […]