A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic neuropathy type V

A boy with recurrent pyrexial episodes from early life sustained a painless ankle injury and was found to have a calcaneus fracture and, later, neurop athic joint degeneration of the tarsus. Examination revealed distal loss of pain and temperature sensation and widespread anhidrosis. Sural nerve biop sy demonstrated severe reduction in small-caliber myelinated fiber density but only modest reduction in unmyelinated axons, the pattern of type V here ditary sensory and autonomic neuropathy (HSAN V). DNA analysis showed that he was homozygous for a mutation in the NTRK1/high-affinity nerve growth fa ctor (TrkA) gene, his parents being heterozygous. Mutations in this gene ar e known to be responsible for HSAN IV (congenital insensitivity to pain wit h anhidrosis). The two disorders are therefore likely to be allelic.