Persistent Neutropenia and Atopy in an Adolescent: A Subtle Presentation of Phosphoglucomutase 3 Deficiency

Phosphoglucomutase 3 (PGM3) deficiency (OMIM (Online Mendelian Inheritance in Man) #615816) is a rare autosomal recessive congenital disorder of glycosylation that disrupts multiple glycosylation pathways, with few cases reported in the literature. It leads to a broad clinical spectrum ranging from hyper-IgE syndrome (HIES)-like features to severe combined immunodeficiency (SCID). We report a case of a 17-year-old female of Brazilian origin, referred to our center in Portugal for investigation of persistent neutropenia. Her medical history included recurrent infections in early childhood, severe eczema, and autism spectrum disorder. She exhibited persistent neutropenia and T-cell lymphopenia, with elevated IgE levels. Genetic analysis using a next-generation sequencing panel for primary immunodeficiencies identified compound heterozygous likely pathogenic variants in PGM3: a missense variant (c.1475C>T, p.(Thr492Ile)) and a complete gene deletion in the other allele, confirming the diagnosis of PGM3 deficiency. Chronic neutropenia was the main finding that prompted the genetic investigation. Although it is not a defining feature of PGM3 deficiency, it has been reported in nearly half of the cases. In this patient, the clinical presentation has been comparatively milder than the severe phenotypes described in the literature, which highlights the phenotypic variability of this condition and the need for clinical suspicion, even when classical features are absent. The genetic diagnosis has important implications for clinical follow-up and enables appropriate genetic counseling. This case illustrates the clinical variability of PGM3 deficiency and reinforces the role of genetic testing in clarifying the diagnosis, guiding management, and informing long-term follow-up in rare inborn errors of immunity.