A case of Wiskott‐Aldrich syndrome with cilial immotility

Abstract

We report the case history of a 25-year-old man who was diagnosed as having Wiskott-Aldrich syndrome in infancy. He had the typical features of severe eczema, thrombocytopenia and recurrent sinopulmonary infection. By his late teenage years he had developed bronchiectasis despite having normal levels of immunoglobulin and IgG subclasses. His functional antibody responses to tetanus toxoid and pneumococcal vaccine were suboptimal (15% and 52% of normal respectively). Regular intravenous immunoglobulin therapy resulted in a reduced frequency and severity of infection but despite this treatment he continued to get respiratory infections. In April 1999 he presented with three episodes of acute gastrointestinal haemorrhage. CT scan of the abdomen and arteriography showed multiple arterial aneurysms with evidence of active haemorrhage within the liver and upper small bowel. Inflammatory markers (ESR and C-reactive protein) were markedly elevated and he was diagnosed as having acute inflammatory vasculitis as a complication of his primary immune disorder.1 Prednisone and cyclophosphamide therapy were deemed necessary to treat the vasculitis and prevent further life-threatening haemorrhage. Before immunosuppressive therapy was started, seminal fluid samples were obtained for storage. Analysis revealed not only a low sperm count (<2 × 106/ml) but also the fact that all spermatozoa were immotile. In order to investigate cilial function more fully, nasal brush biopsy samples were obtained and cilial activity was assessed by a standard method on fresh samples. No evidence of cilial movement was observed in any of the tissue samples. The role of Wiskott-Aldrich Syndrome Protein (WASP) in transmitting signals from CDC42HS to the actin cytoskeleton of cells To our knowledge, this is the first report of cilial immotility as a feature of this condition. Wiskott-Aldrich syndrome is an X-linked primary immunodeficiency disorder characterised by thrombocytopenia, eczema and recurrent infection.2 The gene defect has been identified at the Xp11.22 position on the short arm of the X chromosome and designated the WAS gene.3 A variety of mutations have been described, all of which result in the absence of WAS protein or the production of a functionally defective protein. In normal individuals WAS protein plays a central role in the control of cellular morphology and the organisation of the cytoskeleton of cells.4 Defects in some of these, including actin polymerisation (Figure 1), have been identified and help to explain many of the clinical manifestations of WAS.5 In the past, the increased frequency of infection in this disorder was attributed to impaired antibody production. Some patients, however, including this case, develop sinopulmonary infection and bronchiectasis at an early age which cannot be explained by a defect in antibody production alone and may represent some other defect in the antibacterial defence system of the respiratory tract. It is not clear whether or not cilial immotility occurs in all WAS patients or only in certain genetic variants of the disorder.