Wiskott-Aldrich-Syndrom am Beispiel eines Patienten

Zusammenfassung

Das Wiskott-Aldrich-Syndrom (WAS) gehört zur Gruppe der X-chromosomal gekoppelten primären Immundefektsyndrome und ist charakterisiert durch kongenitale Mikrothrombozytopenie, rekurrierende schwere Infektionen, kombinierte zelluläre und humorale Abwehrschwäche, Ekzem, Malignome und Autoimmunkrankheiten.

Es werden der klinische Verlauf, die hämatologischen, immunologischen und molekulargenetischen Befunde eines Jungen mit schwerem Verlauf eines WAS beschrieben. Neben der charakteristischen Mikrothrombozytopenie war die Thrombozytenfunktion stark beeinträchtigt, die Anzahl der CD3+-T-Zellen erniedrigt, die der CD16+/CD56+-NK-Zellen erhöht. Molekulargenetisch zeigte sich eine bisher nicht beschriebene Spleißstellenmutation im Bereich des Introns 3 des WASP-Gens (IVS3+2t>a). Wir konnten bei dem Patienten zeigen, dass die intrazytoplasmatische γ-Interferon-Bildung in T-Zellen signifikant erhöht ist. Nach einer zunächst erfolgreichen allogenen Stammzelltransplantation starb der Junge an den Komplikationen einer CMV-Pneumonie.

Das WAS ist ein komplexes Krankheitsbild. Der Nachweis einer Mikrothrombozytopenie bei einem Knaben ist immer verdächtig und diagnostisch wegweisend für diese Erkrankung.

Summary

The Wiskott-Aldrich syndrome (WAS) is one of the X-linked immunodeficiency diseases and is characterized by congenital microthrombocytopenia, recurrent infections, combined cellular and humoral immunodeficiency, eczema, malignancies and autoimmune manifestations.

We describe the clinical course, hematologic, immunologic and genetic findings in a patient with a novel splice-site mutation in the WASP gene localized at intron 3 (IVS3+2t>a). The patient exhibited typical microthrombocytopenia, functions of thrombocytes were impaired. CD3+T cells were decreased, CD16+/CD56+ natural killer cells were markedly increased. We found that T cells of the patients showed an increased intracytoplasmic γ-interferon production. Stem cell transplantation from a CMV seropositive allogeneic donor was performed. The boy died after successful initial engraftment due to severe CMV-pneumonia despite antiviral therapy.

WAS is a complex disorder. The demonstration of microthrombocytopenia in male infants is highly suspicious and diagnostic for this rare disease.

Schlüsselwörter

Wiskott-Aldrich-Syndrom - Mikrothrombozytopenie - Mutation - Stammzelltransplantation - CMV

Keywords

Wiskott-Aldrich syndrome - microthrombocytopenia - WASP gene - mutation - stem cell transplantation - CMV

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