Fatal EBV Infection and Variable Clinical Manifestations in an XLP-1 Pedigree – Rapid Diagnosis of Primary Immunodeficiencies may Save Lives

Abstract

Two related boys who died from fulminant infectious mononucleosis were diagnosed with X-linked lymphoproliferative disease type 1 (XLP-1). Family screening (n=17) identified 6 female mutation carriers and 2 more XLP-1 patients in whom, despite recurrent infections, agammaglobulinemia, and Hodgkin’s Disease, the genetic basis had been unknown; demonstrating that awareness and early genetic testing are crucial to reveal underlying primary immunodeficiencies and improve outcome. Furthermore, XLP should be included routinely in the differential diagnosis of severe hypogammaglobulinemia and/or lymphoma in males.

Zusammenfassung

Zwei verwandte Buben verstarben innerhalb von 4 Monaten an fulminant verflaufender infektiöser Mononukleose (FIM). Die genetische Diagnostik ergab eine X-linked lymphoproliferative Erkrankung Typ 1 (XLP-1); im Familienscreening wurden 6 weibliche Mutationsträgerinnen und 2 weitere männliche XLP-1 Patienten mit rezidivierenden Infektionen, Agammaglobulinämie und Hodgkin Lymphom identifiziert. Diese XLP-1 Krankheitsverläufe demonstrieren, dass nicht nur bei FIM an zugrundeliegende Immundefizienzen wie XLP gedacht werden sollte.

Key words

EBV infection - lymphoproliferative disease - primary immunodeficiency - family screening - genetic counselling - hemophagocytic lymphohistiocytosis

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