Phosphoglucomutase 3 (PGM3) deficiency is a rare congenital disorder of glycosylation, characterized by combined immunodeficiency, severe atopy, and variable neurodevelopmental impairment.
To describe the clinical, immunological, and genetic features of three pediatric patients with PGM3 deficiency.
We retrospectively analyzed three pediatric patients with genetically confirmed PGM3 deficiency followed at the Pediatric Department of the National Bone Marrow Transplantation Center in Tunis.
The cohort included two girls and one boy, with a median age at diagnosis of 15 months (range, 9–34 months). All were born to consanguineous parents. Recurrent infections began in early infancy, predominantly lower respiratory tract infections and skin infections secondary to severe eczema. Viral infections were frequent but non–life-threatening; no invasive bacterial sepsis was documented. All patients exhibited severe atopic dermatitis, persistent hypereosinophilia, and elevated serum IgE in two cases. Immunological evaluation revealed reduced total T cell counts (CD3+) in all patients, marked lymphopenia in one child, decreased CD4+ T cells, and preserved CD8+ T cells; B cell counts were normal. One patient had partially impaired functional antibody responses, without severe hypogammaglobulinemia. Genetic analysis identified a homozygous p.Glu340del variant in all patients, suggesting a founder effect. Management included antibiotic prophylaxis, topical corticosteroids, and immunoglobulin replacement in one patient. No patient received hematopoietic stem cell transplantation. Clinical follow-up was notable for persistent severe eczema with recurrent superinfections.
This study underscores the key features of PGM3 deficiency, including severe eczema and frequent infections. The recurrent p.Glu340del variant indicates a potential founder effect in this population. Management remains challenging, highlighting the need for improved strategies, including targeted therapies for eczema and consideration of allogeneic hematopoietic stem cell transplantation.
