Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant

J Pediatr Hematol Oncol. 2024 Aug 1;46(6):e472-e475. doi: 10.1097/MPH.0000000000002862. Epub 2024 May 14.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Agammaglobulinemia / genetics
  • Cardiomyopathy, Hypertrophic / genetics
  • Cardiomyopathy, Hypertrophic / pathology
  • Carrier Proteins / genetics
  • Homozygote*
  • Humans
  • Infant
  • Male
  • Neutropenia / congenital
  • Neutropenia / genetics
  • Neutropenia / immunology

Substances

  • FNIP1 protein, human
  • Carrier Proteins