A Novel Inflammatory Autoimmune-Like NTRK1-Associated Phenotype in an Adult Man

Neurotrophic tyrosine receptor kinase 1 (NTRK1) 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 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.

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 3 years ago after vaccination.

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.