Wiskott-Aldrich Syndrome

This 9-month-old boy was initially evaluated at age 6 weeks for an extensive eczematous rash on the head and antecubital and diaper areas and blood and mucus in the stool with each diaper change over a 2- to 3-week period. The symptoms were attributed to milk allergy, and the infant’s formula was changed. At 8 weeks of age, a petechial rash developed on the boy’s trunk and legs. His symptoms persisted despite multiple formula changes, and he was referred to the emergency department.

A complete blood cell (CBC) count revealed a white blood cell count of 10,200/µL, absolute neutrophil count of 500/µL, hemoglobin level of 10.7 g/dL, and platelet count of 7000/µL. Blood group was O positive, Coomb negative. Results of a coagulation profile and serum chemistries were normal, as were serum immunoglobulin levels. A peripheral blood smear showed a decrease in the number and size of platelets. The mean platelet volume (MPV) on the CBC count was 6.6 fl (normal range, 7.4 to 11.4 fl). The infant received intravenous immunoglobulin (IVIG) and a platelet transfusion.

The platelet count increased to 115,000/µL but dropped within 12 hours to 33,000/µL. Bone marrow was normal. Further immune workup showed a decrease in total T and B cells, with a relative paucity of CD8 lymphocytes and a CD4:CD8 ratio of 6.62.

The infant continued to require platelet transfusions and IVIG every 2 to 3 days. Wiskott-Aldrich syndrome (WAS) was considered the most probable diagnosis in a male infant with severe thrombocytopenia, eczema, and small platelet size. There was no family history of immunodeficiencies. Other differential diagnoses, such as infection, aplastic anemia, inherited and acquired bone marrow failure syndromes, malignancies, and combined immunodeficiency, were excluded. Flow cytometry showed a complete absence of the WAS protein in peripheral blood mononuclear cells. Sequence determination of the WAS protein gene identified a nonsense point mutation (310 C > T) resulting in early termination at amino acid position 104, which confirmed the diagnosis. Absence of the WAS protein correlates with severe phenotype, as was the case in this patient.^1,2

WAS is a rare X-linked recessive disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhea.³ In this syndrome, the platelets are small and function improperly. They are removed by the spleen, which leads to low platelet counts. Autoimmune disorders are also frequently found in patients with WAS.

The combination of eczema and bloody diarrhea is a common presentation in infants and is often attributed to milk allergy. WAS is almost never considered in the initial differential diagnosis. The diagnosis is highly probable when thrombocytopenia is associated with low MPV on CBC count. Serious bleeding and infectious complications in these infants require early consideration of this diagnosis with timely referral to specialists for further management and possible early HLA-matched hematopoietic stem cell transplant—currently the only cure.⁴ A fully matched unrelated donor was identified for this infant, and he underwent bone marrow transplant. He is currently doing well.