Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant

• Published in: Journal of pediatric hematology/oncology Vol. 46; no. 6; pp. e472 - e475
• Main Authors: Ulaş, Selami, Naiboğlu, Sezin, Özyilmaz, İsa, Öztürk Demir, Asli Güner, Turan, Işilay, Yuzkan, Sabahattin, Ayaz, Akif, Çeliksoy, Mehmet Halil
• Format: Journal Article
• Language: English
• Published: United States 01-08-2024
• Subjects: Agammaglobulinemia - genetics; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Carrier Proteins - genetics; Homozygote; Humans; Infant; Male; Neutropenia - congenital; Neutropenia - genetics; Neutropenia - immunology
• ISSN: 1077-4114; 1536-3678; 1536-3678
• DOI: 10.1097/MPH.0000000000002862

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.