Low Incidence of Cryptic Genetic Marrow Failure in Pediatric Severe Aplastic Anemia Following Negative Clinical Workup
In brief
In 113 children with negative workups, sequencing found no hidden marrow-failure syndrome
Among 113 children with severe aplastic anemia and no clinical or laboratory signs of inherited marrow failure, enhanced genetic testing found no diagnostic variants. Two of 36 children with suggestive findings had potentially relevant variants, though one case remained unresolved. The retrospective results suggest treatment need not wait for genetic testing after a comprehensive negative workup, but broader evidence is needed.
- Journal
- Blood (Q1)
- Published
- 28 October 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Jill L O de Jong, Helen D Reed, Melissa Gaviria Garrido, Ashwin Lakshman Koppayi, Youssef Ahmed, Ian Atkinson, et al.
- PMID
- 42949905
- DOI
- 10.1182/blood.2026034684
Why clinicians should know about it
- Picked for Genetics (clinical) (paper of the day, 29 October 2026): Evaluates germline testing yield in pediatric aplastic anemia workup
Abstract
Distinguishing inherited bone marrow failure syndromes (IBMFS) from acquired idiopathic severe aplastic anemia (SAA) impacts treatment decisions and long-term management. The diagnostic evaluation of SAA has evolved with advances in our understanding of IBMFS. The benefit of germline genetic testing to screen for IBMFS in the context of current comprehensive SAA evaluations has not been systematically assessed. Awaiting genetic testing can delay treatment for idiopathic SAA increasing the risk of life-threatening complications. This retrospective study investigates the incidence of cryptic IBMFS among pediatric patients with SAA evaluated with current standard-of-care clinical and laboratory assessments. Enhanced whole exome sequencing tailored to IBMFS genes was conducted for 153 patients with SAA. Comprehensive clinical and laboratory diagnostic data were available for 149 patients. No clinical or laboratory features of an IBMFS were identified in 113 patients (75.8%) and none harbored pathogenic or likely pathogenic variants diagnostic of IBMFS. At least one clinical finding suggestive of an IBMFS was identified in the remaining 36 patients (24.2%). Of these, one harbored a heterozygous pathogenic variant in SAMD9L and had a consistent clinical history. A second patient flagged by clinical evaluation had two pathogenic variants in ERCC6L2, although allelic phasing and therefore affected status could not be determined. For patients with a negative comprehensive workup for SAA utilizing current diagnostic clinical and laboratory evaluations, the risk of a cryptic IBMFS is low. For these patients, the low likelihood of benefit gained by awaiting genetic testing results must be weighed against the risks of treatment delay.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.