Autoimmune Lymphoproliferative Syndrome (ALPS), commonly caused by mutations in the FAS gene, is a disease with variable penetrance. Subjects may be asymptomatic, or they may present with lymphadenopathy, splenomegaly, cytopenias, or malignancy. Prompt recognition of ALPS is needed for optimal management. We describe a multi-generational cohort presenting with clinical manifestations of ALPS, and a previously unreported heterozygous missense variant of uncertain significance in FAS (c.758G >T, p.G253V), located in exon 9. Knowledge of the underlying genetic defect permitted prompt targeted therapy to treat acute episodes of cytopenia. This cohort underscores the importance of genetic testing in subjects with clinical features of ALPS and should facilitate the reclassification of this variant as pathogenic.
X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency caused by mutations in the Bruton Tyrosine Kinase (BTK) gene. Marked neutropenia can be the initial abnormal laboratory finding in patients with XLA who are presenting with their first illness. The two cases presented herein support early consideration of evaluation for primary humoral immune deficiency in previously healthy male patients under the age of 12 months who present with neutropenia in the setting of infection shortly after passively acquired maternal antibody has sufficiently waned. Initial consideration of XLA (or other humoral immune deficiencies) in this particular population of young male neutropenic patients may afford the opportunity to avoid bone marrow biopsy in otherwise stable cases with similar presentations.
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