A novel NTRK1 mutation in a patient with congenital insensitivity to pain with anhidrosis.

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA), also known as Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), is a rare autosomal recessive disorder which affects the peripheral nervous system. CIPA is caused by mutations in the NTRK1 gene located on chromosome 1 (1q21-q22) [1]. Mutations cause a loss of function with subsequent failure of Trk-A/s-NGF signaling. In this report, we describe the case of a Turkish patient with CIPA with a novel homozygous mutation in NTRK1 gene. The patient is a 7-year-old male, who was diagnosed clinically with CIPA at the age of 10 months while being investigated for episodes of high fever and anhidrosis. He had history of numerous hospitalizations due to fever of unknown origin, chronic otitis media and febrile convulsion at the age of 6 months. Results of extensive examinations including karyotype, blood and urine amino acids, TANDEM mass spectrometry, urinary organic acids, uric acid, lactate, pyruvate, ammonia, humoral and cellular immunity, ophthalmic examination, electromyography, brain magnetic resonance imaging and gene analysis for familial Mediterranean fever all were normal. He also had surgery for a tibial fracture that occurred after falling while playing at the age of 5 years. He had a prior history of multiple fractures of the tibia and ankles. These were after minor trauma and there were no signs of pain subsequent to these fractures. Examination at the age of 7 years revealed wide-based ataxic gait, severely delayed speech (produced only simple single words), absent corneal reflex, tongue bleeding due to self-inflicted bites, eczematous lesions in skin folds, gen