Case Report: Hereditary thrombotic thrombocytopenic purpura mimicking immune thrombocytopenia: diagnostic pitfalls of whole-exome sequencing.

Herein, we describe a 22-month-old girl who presented with isolated severe thrombocytopenia (nadir platelet count: 6 × 10⁹/L) without overt microangiopathic hemolysis. The patient exhibited a partial clinical response to both corticosteroids and intravenous immunoglobulin (IVIG). Bone marrow examination showed increased megakaryocytes, with platelet-producing megakaryocytes accounting for 15% of the total megakaryocyte population. Initial whole-exome sequencing (WES) yielded negative findings for definitive pathogenic variants and clinically significant copy number variations (CNVs). Subsequent targeted genetic testing identified compound heterozygous ADAMTS13 variants: a paternally derived heterozygous exon 8 deletion validated by quantitative PCR (qPCR), and a maternally derived heterozygous frameshift mutation c.2764_2767dup (p.Ala923ValfsTer66) in exon 22 confirmed by Sanger sequencing. Functional analysis revealed severely diminished ADAMTS13 activity (0.23%) with undetectable inhibitory antibodies. The patient's family history was remarkable for a first-trimester miscarriage and a previous neonatal death attributed to severe thrombocytopenia complicated by pulmonary hemorrhage. This case highlights two critical diagnostic pitfalls of pediatric hTTP: atypical presentation with isolated thrombocytopenia and misleading partial responsiveness to immunosuppressive therapy. In addition, routine WES has inherent limitations in detecting exon-level CNVs and certain frameshift variants. For children with unexplained recurrent thrombocytopenia and a suggestive familial bleeding history, ADAMTS13 functional assessment and targeted genetic sequencing should be performed promptly, even if initial WES results are unremarkable.