Glycogen Storage Disease Type Ib (GSD-Ib) is a rare autosomal recessive metabolic disorder caused by mutations in SLC37A4, leading to a deficiency in glucose-6-phosphate translocase. This disorder is characterized by impaired glycogenolysis and gluconeogenesis, resulting in clinical and metabolic manifestations. We report a three-month-old Moroccan female patient presenting with doll-like facies, hepatomegaly, dysmorphic features, and developmental delays. Laboratory analysis revealed hypoglycemia, elevated triglyceride levels, hypercalcemia, and neutropenia. Genetic testing confirmed a homozygous pathogenic variant in SLC37A4 and a heterozygous variant of uncertain significance in TBX1. Initial management included a lactose-free and galactose-free diet, multivitamin supplementation, and granulocyte colony-stimulating factor (G-CSF) therapy to address neutropenia. A novel aspect of this case involves hypercalcemia as an unusual finding in GSD-Ib and the co-occurrence of a variant in the TBX1 gene, which is not typically associated with the disease but may contribute to the patient’s clinical presentation. These findings add a new dimension to our understanding of GSD-Ib and suggest potential avenues for future research to elucidate these genetic interactions and their impact on clinical outcomes.

Primary immune regulatory disorders (PIRDs) are a clinically and genetically complex subgroup of inborn errors of immunity. They are characterized by defects in the mechanisms controlling immune tolerance and inflammatory responses. Loss- or gain-of-function mutations can lead to impaired immune tolerance or exaggerated immune activation, resulting in a broad spectrum of phenotypes that include recurrent infections, lymphoproliferation, autoinflammation, and refractory autoimmunity, particularly autoimmune cytopenias. Through two illustrative pediatric cases, we highlight the diagnostic challenges faced when managing children with unexplained autoimmune cytopenias. In both patients, an initial presentation with autoimmune cytopenia ultimately led, after significant diagnostic delays, to the identification of distinct underlying PIRDs: autoimmune lymphoproliferative syndrome (ALPS) in one case and lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency in the other. These cases underscore the importance of early recognition and comprehensive immunological evaluation to facilitate timely genetic diagnosis and guide targeted therapeutic strategies.