Immunodeficiency Disorders
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Direct answer
Recurrent bacterial sinopulmonary infections beginning after six months of age, when maternal immunoglobulin G wanes, point to antibody deficiency such as Bruton X-linked agammaglobulinaemia, in which B cells and tonsils are absent; recurrent viral, fungal and opportunistic infections with failure to thrive point to T-cell or combined deficiency such as severe combined immunodeficiency or DiGeorge syndrome; catalase-positive staphylococcal abscesses point to chronic granulomatous disease of phagocytes; and recurrent neisserial infection points to late complement defects. Secondary immunodeficiency — malnutrition, human immunodeficiency virus, measles, diabetes, corticosteroids — is far commoner than all primary forms together, and in India the first clue to severe combined immunodeficiency is often a BCG scar that will not heal.
What you must remember
- Bruton disease: X-linked, absent B cells with absent tonsils and lymphoid follicles; recurrent encapsulated bacterial infections from around six months; treated with regular immunoglobulin replacement.
- Severe combined immunodeficiency: the commonest form is X-linked common gamma-chain deficiency; adenosine deaminase deficiency is notable in India, where accumulated deoxyadenosine metabolites poison lymphocytes and gene therapy and enzyme replacement both exist; BCG given at birth can disseminate — BCGitis is often the presenting illness of an Indian infant with SCID.
- DiGeorge syndrome: 22q11.2 deletion — thymic aplasia with low T cells, parathyroid aplasia with neonatal hypocalcaemia, and conotruncal heart defects; the classic viva triad.
- Common variable immunodeficiency: the commonest symptomatic primary antibody deficiency presenting in adults, with low immunoglobulins, recurrent sinopulmonary infection, granulomas and lymphoma risk.
- Wiskott-Aldrich syndrome: X-linked thrombocytopenia with characteristically small platelets, eczema and recurrent infection.
- Chronic granulomatous disease: absent nicotinamide adenine dinucleotide phosphate oxidase burst; the nitroblue tetrazolium test or dihydrorhodamine flow cytometry is diagnostic; infections with catalase-positive organisms — Staphylococcus aureus, Serratia, Aspergillus — and granuloma formation; BCG strain also causes disease.
- Leucocyte adhesion deficiency type 1: delayed separation of the umbilical cord with absent pus — a one-line diagnosis in vivas.
- HIV disease: CD4 T-cell destruction, AIDS defined below 200 cells per microlitre, with the wasting, opportunistic infections and tumours; secondary immunodeficiency from malnutrition remains numerically the world's commonest.
An Indian infant whose BCG scar misbehaved
A four-month-old, born normally and given BCG on day one, returns with an ulcerated axillary node draining for six weeks, persistent oral thrush and intractable diarrhoea, weight falling off the curve. Each finding alone is ordinary in Indian practice; together they are the entry point to severe combined immunodeficiency. The reasoning moves outward: thrush and diarrhoea suggest T-cell dysfunction, the disseminated BCG confirms profound cellular immune failure (live attenuated vaccines — BCG, oral polio, rotavirus — are the first pathogens of an undiagnosed SCID infant), and the next tests are a full blood count with a lymphocyte count, then flow cytometry for CD3, CD4, CD8, CD19 and CD16/56 to place the defect, with immunoglobulin levels alongside.
If lymphocytes are globally low with absent T and natural killer cells and normal B cells, X-linked common gamma-chain disease leads the list; if the metabolite screen shows raised deoxyadenosine, adenosine deaminase deficiency does — a form disproportionately reported from India, treated historically with pegylated enzyme replacement and now with gene therapy in centres abroad. Management until definitive stem-cell transplantation is protective isolation, prophylactic co-trimoxazole and antifungals, irradiated cytomegalovirus-negative blood products, and live vaccine avoidance for the infant and oral polio avoidance for household contacts. The general lesson generalises: treat any infection that is unusually persistent, unusually located or caused by an unusually weak organism as a question about the immune system.
Where students slip
The reflex error is labelling every child with repeated coughs immunodeficient — most recurrent infections in Indian children reflect exposure, crowding, malnutrition or asthma, and the screening cascade begins simply: full blood count, immunoglobulins, HIV serology, blood film. Second, the deficiencies get shuffled — Bruton has absent B cells but a normal thymus and normal T cells, so viral defences are intact; DiGeorge is the mirror image. Third, candidates forget that malnutrition and HIV, not any primary syndrome, make up the overwhelming majority of immunodeficiency, a sentence that earns marks precisely because national examinations reward public-health framing.
Frequently asked questions
Which deficiency causes bacterial infections only after the first six months?
Bruton X-linked agammaglobulinaemia — maternal immunoglobulin G protects until it wanes; tonsils and B cells are absent.
Which enzyme is deficient in adenosine deaminase SCID?
Adenosine deaminase, whose accumulated toxic metabolites destroy T and B lymphocytes; options include enzyme replacement and gene therapy.
Which test screens for chronic granulomatous disease?
The nitroblue tetrazolium test or dihydrorhodamine oxidation assay, demonstrating the absent oxidative burst; infections are with catalase-positive organisms.
Which immunodeficiency presents with delayed umbilical cord separation?
Leucocyte adhesion deficiency type 1, from absent CD18 integrins, with absent pus despite infection.
What is the triad of DiGeorge syndrome?
Thymic aplasia with T-cell deficiency, parathyroid aplasia with hypocalcaemia, and conotruncal cardiac defects, from 22q11.2 deletion.
Which is the commonest immunodeficiency overall?
Secondary immunodeficiency — malnutrition worldwide, and human immunodeficiency virus infection — not any primary syndrome.