Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant

This is the authors' abstract. We don't add key points for this paper.

Agammaglobulinemia represents the most profound primary antibody deficiency, stemming from early cessation of B-cell development. Deficiency in folliculin-interacting protein 1 (FNIP1) is a novel inborn error of immunity characterized by a severe defect in B-cell development, agammaglobulinemia, variable neutropenia, and hypertrophic cardiomyopathy. FNIP1 plays a critical role in B-cell development and metabolic homeostasis, establishing a metabolic checkpoint that ensures pre-B cells possess sufficient metabolic capacity to undergo division while concurrently limiting lymphogenesis due to abnormal growth. Disruption of FNIP1 functionality affects the fundamental metabolic regulators adenosine monophosphate-activated protein kinase and mTOR, culminating in a severe B-cell deficiency alongside hypogammaglobulinemia, hypertrophic cardiomyopathy, preexcitation syndrome, and intermittent neutropenia. This case report presents an 11-month-old male patient with FNIP1 deficiency who, in addition to classical features, exhibited posterior cerebellar hypoplasia.