Genomic diagnosis and multisystem phenotyping in pediatric congenital analbuminemia: clinical, coagulation, and immune signatures.

Background: Congenital analbuminemia (CAA) is an ultrarare autosomal recessive disorder caused by biallelic pathogenic variants in the Methods: We conducted a longitudinal integrative study involving five children from two kindreds, all with genetically confirmed CAA. Their clinical features were thoroughly documented, along with extended coagulation tests and immunological profiling. Results: All patients presented with persistent hypoalbuminemia, early-onset edema, gastrointestinal morbidity (frequently leading to misdiagnosis as protein-losing enteropathy), antenatal complications, recurrent respiratory infections, and dyslipidemia. Genetic testing revealed an Conclusions: This study provides detailed multisystem phenotyping of pediatric CAA and supports the view that CAA may present with clinically relevant gastrointestinal, metabolic, infectious, and hemostatic manifestations beyond isolated hypoalbuminemia. Early molecular diagnosis may reduce unnecessary invasive investigations and facilitate individualized monitoring for infectious and thrombotic complications. Larger multicenter studies with longitudinal follow-up and functional validation are required to confirm these findings.