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Autoimmune lymphoproliferative syndrome (ALPS): Epidemiology and pathogenesis

Author
Jack JH Bleesing, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by dysregulation of the immune system, due to an inability to regulate lymphocyte homeostasis through the process of lymphocyte apoptosis (a form of programmed cell death). The consequences of this include lymphoproliferative disease, manifested by lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma, as well as autoimmune disease, typically involving blood cells.

Several genetic defects are associated with ALPS. ALPS-FAS and ALPS-sFAS are caused by germline and somatic mutations in the FAS gene, respectively. In rare cases, ALPS is caused by mutations in the genes encoding Fas ligand (ALPS-FASLG) or caspase 10 (ALPS-CASP10).

This topic reviews the epidemiology, genetics, and pathogenesis of ALPS. The clinical manifestations, laboratory findings, diagnosis, and management of ALPS is discussed separately. (See "Autoimmune lymphoproliferative syndrome (ALPS): Management and prognosis" and "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis".)

EPIDEMIOLOGY

The incidence and prevalence of ALPS are unknown. Estimated cases of ALPS worldwide exceed 500, but that number has not reliably been confirmed. Cases of ALPS probably remain undiagnosed due to variable phenotypic expression and a constellation of symptoms that overlap with many other conditions, particularly Evans' syndrome and other lymphoproliferative disorders [1,2]. (See "Warm autoimmune hemolytic anemia: Clinical features and diagnosis", section on 'Evans syndrome' and "Autoimmune hemolytic anemia in children: Classification, clinical features, and diagnosis", section on 'Evans syndrome'.)

ALPS is reported in various racial and ethnic backgrounds. A male predominance was previously suggested. [3]. This gender inequality was confirmed in the French ALPS cohort and the National Institutes of Health (NIH) ALPS cohort [4,5]. In families with FAS mutations in the French cohort, the likelihood that a male developed ALPS was about 75 percent, compared with 51 percent for females, while the NIH cohort showed a 69 percent and 46 percent likelihood of developing ALPS for males and females, respectively. In addition, the ratio of male to female patients with ALPS was 2.2 (French cohort) and 1.6 (NIH cohort).

     

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Literature review current through: Nov 2016. | This topic last updated: Tue Jan 19 00:00:00 GMT+00:00 2016.
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