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

Distinguishing an inherited bone marrow failure syndrome from acquired idiopathic severe aplastic anemia drives treatment, but awaiting genetic results can delay care. This retrospective study performed exome sequencing enhanced for inherited bone marrow failure genes in 153 children with severe aplastic anemia, 149 of whom had complete clinical and laboratory data. None of the 113 patients (75.8%) without clinical or laboratory features of inherited marrow failure carried a diagnostic pathogenic or likely pathogenic variant. Among the 36 patients (24.2%) with at least one suggestive finding, one carried a heterozygous pathogenic SAMD9L variant with a consistent clinical history, and another had two pathogenic ERCC6L2 variants whose phase could not be determined.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A negative but directly useful result: after a complete negative clinical and laboratory workup, the risk of cryptic inherited marrow failure in children is low, and waiting for genetic results must be weighed against the risk of delaying treatment. Genetic testing keeps its place, but its yield concentrates in patients with at least one red flag. Limitation: a retrospective study of modest size, in which the absence of diagnosis in 113 patients does not rule out a low but real risk.

Analysis by Dr Thibaut Benquey