Low Incidence of Cryptic Genetic Marrow Failure in Pediatric Severe Aplastic Anemia Following Negative Clinical Workup.

In 153 pediatric severe aplastic anemia patients evaluated with current clinical and laboratory workup, cryptic inherited bone marrow failure syndromes were found in 24.2%, with none in 75.8%.

• Why it matters: Distinguishing inherited marrow failure from acquired idiopathic SAA affects treatment and long-term management, but the value of germline genetic screening after modern SAA evaluation is not well quantified.
• What they did: This retrospective study used enhanced whole exome sequencing focused on IBMFS genes in 153 patients, with complete clinical and laboratory data for 149.
• The result: Among 113 patients (75.8%) with no IBMFS features, none had pathogenic or likely pathogenic IBMFS variants; among 36 (24.2%), one had a pathogenic SAMD9L variant and another had two pathogenic ERCC6L2 variants with uncertain phasing.