Cureus. 2025 Dec;17(12):
e99572
Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency characterized by microthrombocytopenia, recurrent infections, eczema, and risk of autoimmunity or malignancy. Ghoshal hematodiaphyseal dysplasia (GHD) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the TBXAS1 gene, leading to bone marrow fibrosis, transfusion-dependent anemia, and skeletal dysplasia. While each disorder individually is rare, their co-inheritance in the same patient has not been reported. With the increasing use of next-generation sequencing, dual genetic diagnoses are being recognized, particularly in consanguineous populations, and often present with blended phenotypes that complicate diagnosis and management. We describe a 14-month-old boy, the third child of consanguineous parents, presenting with transfusion-dependent anemia from early infancy, severe thrombocytopenia with microplatelets, recurrent bacterial infections, mild splenomegaly, and evidence of early marrow fibrosis. Genetic testing revealed a hemizygous frameshift mutation in the WAS gene (c.511del; p.Arg171GlufsTer90) consistent with WAS, along with a homozygous missense mutation in TBXAS1 (c.1235G>A; p.Arg412Gln), confirming GHD. Both variants were classified as pathogenic. The co-inheritance necessitated modification of treatment for both individual diseases. Supportive care with transfusions and antimicrobials was provided. This case highlights the first and exceptional occurrence of two rare inherited disorders: WAS and GHD in the same child. The blended phenotype, with early marrow fibrosis, could not be explained by either condition alone. Such dual diagnoses underscore the critical role of molecular testing in atypical pediatric cytopenias.
Keywords: bone marrow fibrosis; dual mutation; ghoshal hematodiaphyseal dysplasia; immunodeficiency; inherited anemia; wiskott-aldrich syndrome