Unmasking Wiskott–Aldrich Syndrome in Adulthood in a Case of Long-Standing Bleeding, Infections, and Steroid-Induced Morbidity

TL;DR

A 28-year-old man was diagnosed with Wiskott-Aldrich syndrome after years of misdiagnosis and steroid treatment for symptoms resembling immune thrombocytopenia.

Contribution

This case highlights the atypical adult presentation of Wiskott-Aldrich syndrome and the importance of genetic testing for accurate diagnosis.

Findings

The patient had a hemizygous pathogenic nonsense variant in the WAS gene, confirming the diagnosis.

Prolonged steroid use led to iatrogenic Cushing’s syndrome despite treatment for presumed immune thrombocytopenia.

Family history of consanguinity and recurrent infections supported an inherited immunodeficiency diagnosis.

Abstract

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by the classic triad of microthrombocytopenia, recurrent infections, and eczema, with most cases diagnosed during infancy or early childhood. Adult presentation is uncommon and often leads to diagnostic delay or misdiagnosis. We report the case of a 28-year-old male who presented with multiple episodes of bleeding, petechiae, recurrent skin and respiratory infections, and chronic eczematous lesions. Over several years, he underwent repeated hospitalizations and was treated for immune thrombocytopenia (ITP) with prolonged courses of oral corticosteroids, resulting in features of iatrogenic Cushing’s syndrome, including moon facies and skin thinning. Despite steroid therapy, his symptoms worsened, and he continued to have intermittent respiratory tract infections, urinary tract infections, and recurrent skin ulcers. The patient’s family history revealed consanguinity and recurrent infections among female relatives, including his mother and maternal aunt, raising suspicion for an inherited immunodeficiency. On examination, he had diffuse eczematous lesions over the hands and feet, petechiae, and Cushingoid features. Laboratory investigations showed persistent thrombocytopenia with a low mean platelet volume, elevated inflammatory markers, and evidence of immune dysregulation. Given the constellation of symptoms, a primary immunodeficiency was suspected, prompting genetic evaluation. Whole-exome sequencing identified a hemizygous pathogenic nonsense variant in the WAS gene: NM_000377.3; chrX:48688689; c.961C>T; p.Arg321* in exon 10, confirming the diagnosis of WAS. This variant is predicted to result in the premature truncation of the WAS protein and is consistent with a classical WAS phenotype. This case highlights the challenges in diagnosing WAS in adulthood, especially when initial symptoms mimic more common hematological conditions such as ITP. Early recognition of syndromic features and consideration of inherited immunodeficiencies in persistent thrombocytopenia with eczema can prevent prolonged steroid exposure and facilitate timely, appropriate management.

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