GATA2 deficiency predisposes patients to recurrent infections, myelodysplastic neoplasms (MDSs), and malignancies through disrupted hematopoiesis and immune dysfunction. The role of the gut microbiome (GM) in this condition remains poorly defined. In this multicenter study, we analyzed GM composition, metabolomic, and lipidomic profiles in 12 Italian GATA2-deficient patients, comparing non-HSCT and post-HSCT GATA2-deficient individuals with healthy controls. Non-HSCT patients showed a relative enrichment of Proteobacteria-associated Gram-negative taxa, accompanied by increased levels of metabolites and lipids previously associated with inflammatory processes. Post-HSCT patients displayed profiles with a trend toward partial normalization of GM composition and metabolic features. Overall, our findings suggest the presence of microbiome and metabolic patterns in GATA2-deficient patients, which may reflect underlying immune and hematopoietic alterations, although these observations should be interpreted as descriptive and require validation in larger cohorts.

Folliculin-interacting protein 1 (FNIP1) is a key regulator of cellular metabolism and immune homeostasis, integrating nutrient signaling with proteostasis. FNIP1 forms a complex with folliculin (FLCN) to regulate the mechanistic target of rapamycin complex 1 (mTORC1), functioning as a GTPase-activating protein (GAP) for RagC/D. Additionally, FNIP1 interacts with heat shock protein 90 (HSP90) and undergoes phosphorylation, glycosylation, and ubiquitination, which dynamically regulate its stability and function. Evidence from murine models suggests that FNIP1 loss disrupts immune cell development and mitochondrial homeostasis. However, FNIP1 deficiency in humans remains incompletely characterized, and its full phenotypic spectrum is likely underestimated. Notably, FNIP1-deficient patients exhibit immunological and hematological abnormalities, immune dysregulation, and metabolic perturbations, emphasizing its role in cellular adaptation to stress. Understanding the mechanistic basis of FNIP1 dysfunction in human tissues will be critical for delineating its contributions to immune and metabolic disorders and identifying targeted interventions.

A 9-month-old infant, the second child in the family, presented to the emergency room with a persistent fever lasting six days, accompanied by cough, runny nose and stomatitis. Initial examination revealed generalised malaise, irritability, bilateral periorbital oedema, ulcerative lesions on the tonsils, erythematous oropharynx and a maculopapular rash predominantly on the face and trunk. Laboratory tests showed mild thrombocytopenia and elevated inflammatory markers but normal hepatic and renal function. A chest X-ray was unremarkable. The child was admitted for observation and broad-spectrum intravenous antibiotics. After 24 hours, measles was suspected due to the clinical presentation, confirmed by serology (positive IgM and negative IgG). Supportive treatment continued, and the child was discharged after five days with improved clinical status. The case highlights an ongoing global increase in measles incidence, attributed to suboptimal vaccination coverage and vaccine hesitancy. It underscores the necessity for timely recognition and isolation of suspected cases and emphasises prevention through vaccination, as incidence rates among unvaccinated children remain high. The experience also calls for heightened awareness in the medical community regarding the resurgence of measles.

HF is a full-term newborn, third child of consanguineous parents from Bangladesh. In good general health at birth, she developed significant hyperbilirubinemia within the first 48 hours of life and required phototherapy (PT), with a total of nine treatment cycles needed. As jaundice persisted for over 2 weeks, first-level laboratory and imaging investigations were performed to exclude cholestatic, metabolic and/or infectious causes and their results were normal. Given the negative findings, the persistence of jaundice and the parents’ consanguinity, a genetic analysis was performed and showed two monoallelic variants in the UGT1A1 gene, potentially associated with transient familial neonatal hyperbilirubinemia. Subsequently, bilirubin levels spontaneously normalised by 3 months of age, as showed by the molecular analysis. The described case highlights the need for a systematic diagnostic approach in prolonged jaundice, the added value of genetic testing for clarifying the cause of unclear clinical presentations and provides useful information for pre-conception genetic counselling.