Supplementary Material for: A novel inflammatory autoimmune-like NTRK1-associated phenotype in an adult man

Introduction: NTRK1 (Neurotrophic Tyrosine Receptor Kinase 1) encodes a 796 amino acid long transmembrane nerve growth factor (NGF) receptor, which is abundantly expressed in neuromuscular tissues. Deficiency of NTRK1 is typically clinically presented as autosomal recessive infantile Congenital Insensitivity to Pain with Anhidrosis (CIPA), characterized by decreased pain and temperature perception, anhidrosis and, sometimes, by an intellectual disability and a premature death. So far, over 170 different NTRK1 mutations have been reported in the literature, including the missense disease-causing variants p.R748W. Case presentation: In this case report we present a 40-year-old man with CIPA based on the known and novel heterozygous p.R748W and c.575-15G˃A NTRK1 mutation, respectively. This man exhibited progressive arthralgias, bursitis, folliculitis, fatigue and pancreatitis with a slight variation of some immunological parameters, that started about three years ago after vaccination. Conclusion: The finding of an inflammatory autoimmune-like disease in the presented 40-year-old patient with a normal intelligence and a reduced sweating and pain sensation indicates that this phenotype represents, besides the typical serious infantile CIPA, a novel adult-onset clinical expression of the NTRK1-induced disease. In addition, the data here also support the recent suggestion that the defective NGF signaling of the neural, immune and endocrine systems in CIPA may link this congenital disease to autoimmunity.