Gray platelet syndrome can mimic autoimmune lymphoproliferative syndrome

A Rensing-Ehl, U Pannicke… - Blood, The Journal …, 2015 - ashpublications.org
A Rensing-Ehl, U Pannicke, SY Zimmermann, MR Lorenz, B Neven, I Fuchs, U Salzer…
Blood, The Journal of the American Society of Hematology, 2015ashpublications.org
The combination of splenomegaly and autoimmune cytopenia is frequently associated with
primary immunodeficiencies. The most frequent disease is autoimmune lymphoproliferative
syndrome (ALPS), caused by autosomal dominant germline or somatic mutations of the FAS
gene. 1, 2 The differential diagnosis can be challenging, but the combination of serum
vitamin B12 and soluble FAS ligand (sFASL) has a high predictive value for the presence of
FAS mutations and is currently used for screening. We report 2 siblings of a consanguineous …
The combination of splenomegaly and autoimmune cytopenia is frequently associated with primary immunodeficiencies. The most frequent disease is autoimmune lymphoproliferative syndrome (ALPS), caused by autosomal dominant germline or somatic mutations of the FAS gene. 1, 2 The differential diagnosis can be challenging, but the combination of serum vitamin B12 and soluble FAS ligand (sFASL) has a high predictive value for the presence of FAS mutations and is currently used for screening.
We report 2 siblings of a consanguineous family referred for suspected ALPS with splenomegaly, thrombocytopenia (patient [P] 1) or pancytopenia (P2), and multiple autoantibodies (Table 1). Screening of another sister revealed a previously unknown thrombocytopenia. Both parents were healthy. Biomarker screening showed vitamin B12 and sFASL levels significantly above the previously defined cutoff values for all 3 affected siblings but not for the unaffected family members. However, no FAS mutation could be found. In addition, normal interleukin-10 levels, only moderate elevation of double-negative T cells (DNT), and normal FAS-mediated
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