Genetic screening of children with marrow failure. The role of Primary Immunodeficiencies.

The differential diagnosis of marrow failure (MF) is crucial in the diagnostic work-up, since genetic forms require specific care. We retrospectively studied all patients with single/multi-lineage MF evaluated in a single-center to identify the type and incidence of underlying molecular defects. The diepoxybutane test was used to screen Fanconi Anemia. Other congenital MFs have been searched using Sanger and/or Next Generation Sequencing analysis, depending on the available tools over the years. Between 2009-2019, 97 patients (aged 0-32 years-median 5) with single-lineage (29%) or multilineage (68%) MF were evaluated. Fifty-three (54%) and 28 (29%) were diagnosed with acquired and congenital MF, respectively. The remaining 16 (17%), with trilinear (9) and monolinear (7) MF, were found to have an underlying primary immunodeficiency (PID) and showed clinical and biochemical signs of immune-dysregulation in 10/16 (62%) and in 14/16 (87%) of cases, respectively. Clinical signs were also found in 22/53 (41%) and 8/28 (28%) patients with idiopathic and classical cMF, respectively. Eight out of 16 PIDs patients were successfully transplanted, 4 received immunosuppression, 2 didn't require treatment, and the remaining 2 died. We show that patients with single/multi-lineage MF may have underlying PIDs in a considerable number of cases and that MF may represent a relevant clinical sign in patients with PIDs, thus widening their clinical phenotype. An accurate immunological work-up should be performed in all patients with MF, and PID-related genes should be considered when screening MF in order to identify disorders that may receive targeted treatments and/or appropriate conditioning regimen before transplant. This article is protected by copyright. All rights reserved.