Correct Answer: C. Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency characterized by the classic triad of thrombocytopenia, eczema, and recurrent infections. The defect lies in the WASp (Wiskott-Aldrich syndrome protein) gene, affecting cytoskeletal organization in hematopoietic cells. Thrombocytopenia is typically severe (platelet count <50,000/μL) with microcytic platelets (mean platelet volume <5 fL), distinguishing it from other syndromes. The immunodeficiency is combined (T-cell and B-cell dysfunction), leading to recurrent bacterial, viral, and opportunistic infections. Eczema is a prominent dermatologic feature. Patients also have increased risk of autoimmune phenomena and malignancy (lymphoma, leukemia). The diagnosis is confirmed by low platelet count with small platelet size and genetic testing for WASp mutations. Management includes prophylactic antibiotics, immunoglobulin replacement, and hematopoietic stem cell transplantation (HSCT) as the only curative option in India, though availability remains limited. The prognosis without HSCT is poor, with median survival around 5–10 years due to infections and bleeding complications.
Why the other options are wrong
A. Chediak-Higashi syndrome — Chediak-Higashi syndrome presents with thrombocytopenia and recurrent infections due to neutrophil dysfunction (giant lysosomal granules), but eczema is NOT a cardinal feature. Instead, patients have oculocutaneous albinism, photophobia, and nystagmus. The triad of thrombocytopenia + eczema + infections is pathognomonic for WAS, not CHS. NBE may use CHS as a distractor because both cause immunodeficiency and infections. B. Hermansky-Pudlak syndrome — Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism and bleeding tendency (platelet dysfunction, not thrombocytopenia), but eczema and recurrent infections are NOT typical features. It is a storage pool disease affecting platelet dense granules. The absence of the eczema-infection triad and the mechanism of bleeding (qualitative platelet defect, not quantitative) make this incorrect. D. Thrombocytopenia–absent radius syndrome — TAR syndrome presents with thrombocytopenia and skeletal abnormalities (absent radii, thumb present), but eczema and recurrent infections are NOT features. It is an autosomal recessive disorder with normal immune function. The absence of immunodeficiency and eczema, combined with the presence of characteristic skeletal findings, distinguishes it from WAS.
High-Yield Facts
- WAS triad: thrombocytopenia (microcytic platelets <5 fL) + eczema + recurrent infections (combined immunodeficiency).
- X-linked recessive inheritance — affects males; females are carriers but may show mild symptoms due to skewed X-inactivation.
- Platelet size is diagnostic — microcytic platelets (MCV <5 fL) in WAS vs. normal-sized platelets in other thrombocytopenia syndromes.
- HSCT is the only curative therapy — allogeneic hematopoietic stem cell transplantation offers long-term survival; gene therapy emerging in select centers.
- Increased malignancy risk — lymphoma and leukemia develop in 10–15% of WAS patients, especially if untreated.
- Autoimmune complications — hemolytic anemia, vasculitis, and arthritis occur in 50% of patients due to dysregulated immune response.
Mnemonics
WAS = Wiskott-Aldrich Syndrome Wiskott = Wet (eczema, wet skin), Aldrich = Anemia/Antibody deficiency (infections), S = Small platelets. Remember: wet skin + infections + small platelets = WAS. Microcytic Platelets = WAS When you see thrombocytopenia + eczema + infections, always check platelet size. If MCV <5 fL (microcytic), it's WAS. Other syndromes have normal or large platelets.
NBE Trap
NBE pairs Chediak-Higashi syndrome with thrombocytopenia and infections to trap students who focus only on the immunodeficiency component and forget that CHS presents with albinism, not eczema. The eczema + thrombocytopenia + infections triad is pathognomonic for WAS.
Clinical Pearl
In Indian pediatric practice, any male child presenting with the triad of thrombocytopenia (with microcytic platelets), eczema, and recurrent infections should prompt immediate WAS workup and referral to a tertiary center for HSCT evaluation. Early diagnosis and transplantation before opportunistic infections or malignancy develop significantly improve outcomes.
_Reference: Robbins Ch. 6 (Genetic Disorders); Harrison Ch. 372 (Primary Immunodeficiencies); OP Ghai Ch. 8 (Immunodeficiency Disorders)_