ATYPICAL PRESENTATION OF WISKOTT-ALDRICH SYNDROME - DIAGNOSIS IN 2 UNRELATED MALES BASED ON STUDIES OF MATERNAL T-CELL X-CHROMOSOME INACTIVATION

  • 15 June 1990
    • journal article
    • research article
    • Vol. 75  (12) , 2369-2374
Abstract
Congenital thrombocytopenia may occur isolation or accompanied by eczema and immunodeficiency, as part of the X-linked hereditary Wiskott-Aldreich syndrome (WAS). Because the clinicaland immunologic picture of WAS is variable, particularly early in life, definite diagnosis cannot always be made in cases with a negative family hisotry. Two unrelated males with sporadic congential thrombocytopenia had only questionable immunologic abnormalities as infants, making them clinically indistinguishable from cases of isolated thrombocytopenia, although one develoed episodic neutroepnia and the other began to manifest a multisystem autoimmune disease at 2 years of age. Evaluation of X chromosome inactivation in the T clels of both patients'' mothers showed each of these women to have the same highly skewed X chromosome inactivation pattern seen in carriers of typical familial WAS. A T-cell defect was subsequently directly demonstrated in the second patient, whose lymphocytes failed to proliferate to perodate and anti-CD43. Taken together, these data suggest the presence of T cell immunodeficiency consistent with WAS in these patients. Furthermore, their mothers were found to have a very high likelihood of being carriers, lending support to the diagnosis of a herediatary disease in these boys and making possible genetic prediction in other family members and subsequent pregnancies.