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Wiskott-Aldrich syndrome: clinical, immunological, and genetic characterization of the first Moroccan cohort.

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PMID42609517
JournalFrontiers in pediatrics
Publication Date2026-08-03
Ingested2026-08-19 09:15 AM
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BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked inborn error of immunity characterized by thrombocytopenia, eczema, and recurrent infections, with additional risks of autoimmunity and malignancy. Country-level data from North Africa are scarce. We report the first genetically confirmed Moroccan series of WAS, describing diagnostic pitfalls, clinical spectrum, and molecular findings. METHODS: We conducted a mixed retrospective-prospective observational cohort study of male patients with molecularly confirmed Wiskott-Aldrich syndrome managed at a Moroccan tertiary referral center between January 2017 and September 2024. Clinical features, hematologic and immunologic data, management, and outcomes were collected from hospital records and available follow-up. RESULTS: Ten male patients were included. Thrombocytopenia was present in all patients (100%), followed by recurrent infections in 9/10 patients (90%) and eczema (90%). Autoimmune complications occurred in 2/10 patients (20%), manifesting as systemic lupus erythematosus with lupus-nephritis-compatible disease in one case and autoimmune hemolytic anemia in the other. Mean platelet volume (MPV) was available in 9/10 patients and was reduced in 2/9 (22.2%). Molecular analysis identified seven distinct pathogenic/likely pathogenic variants: two nonsense (p.Gly322* and p.Arg321*), one splice-site (c.735-2A > T), two frameshift (p.Pro330Leufs*115 and p.Arg431Serfs*64), and two missense (p.Val50Asp and p.Phe128Cys). The p.Gly322* variant recurred in three related patients, including twin brothers, while c.735-2A > T was found in two unrelated individuals, highlighting both familial recurrence and allelic heterogeneity. Truncating and splice-site variants predominated in this cohort (8/10, 80%), consistent with previously reported classic WAS cohorts. One child underwent hematopoietic stem cell transplantation (HSCT) abroad with sustained remission, whereas the others remain on supportive therapy with intravenous immunoglobulin and antimicrobial prophylaxis. CONCLUSIONS: This first genetically confirmed Moroccan case series expands the clinical and molecular spectrum of Wiskott-Aldrich syndrome in North Africa. Our findings highlight the marked clinical and genetic heterogeneity of WAS and underscore the importance of early molecular diagnosis to guide appropriate management, genetic counseling, and timely referral for curative therapy in resource-limited settings.

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Wiskott-Aldrich syndrome: clinical, immunological, and genetic characterization of the first Moroccan cohort.

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