LAUSR

Dear Editor, Congenital insensitivity to pain and anhidrosis (CIPA), also termed as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterised by generalised lack of pain sensation, inability to sweat (anhidrosis) and recurrent episodes of hyperpyrexia. In addition, they can have variable intellectual disability, self-mutilating behaviour, corneal ulcerations and skeletal complications [1]. Mutations in Neurotrophic Tyrosine Receptor Kinase 1 (NTRK1) gene in chromosome 1q21–q22 is responsible for this autosomal recessive (AR) inherited disorder. The clinical manifestations are due to the loss of small myelinated and unmyelinated fibres of peripheral nerves which convey sensation of pain and temperature and sympathetic innervation of eccrine sweat glands [1, 2]. Recurrent non-healing skin ulcers, osteomyelitis, bone fractures, joint deformities and auto-amputation of digits are catastrophic effects of this rare disorder [3]. Herein, we report a case of CIPA to highlight the difficulties in diagnosis and management of complications that can result from lack of pain perception and trophic support. A 3.5-year-old girl presented to us with recurrent injuries and fluctuations in her body temperature since infancy. She was born to third-degree consanguineous parents following an uncomplicated pregnancy and was the youngest of three siblings. From 2 months of age, she had frequent febrile episodes for which no aetiology could be attributed in spite of extensive investigations. Her parents noted that she did not respond emotionally or by withdrawal response to painful stimuli like injections or any accidental trauma. She sustained unnoticed injuries over elbow, forearm, knees and toes leading to nonhealing ulcers, some of which resulted in bone erosion and chronic osteomyelitis. She had decreased sweating despite hot climate. No self-mutilating behaviour was noticed. She was developmentally normal except for a mild delay in gross motor milestones with independent walking achieved at 24 months of age. No other members in her family had similar complaints. Examination showed microcephaly, mild facial dysmorphism (low set ears, anteverted nares and sparse eyebrows) and dystrophic teeth with healed lingual scar. Her hair was dull and lustreless and oral mucosa was dry, but tearing was normal. Corneal reflex was absent. She had a large nonhealing ulcer on her right elbow and a deformed left elbow joint. There were chronic non-healing ulcers of toes of both feet with self-amputation of right great toe with discharging pus and unhealthy granulation (Fig. 1). She had hypotonia of all limbs and generalised areflexia. She had complete absence of pain perception and was unable to appreciate hot or cold stimuli; however, fine touch and vibration were preserved. There was absent flare reaction and no perspiration. Evaluation showed nutritional anaemia and other routine laboratory parameters were normal. The motor and sensory nerve conduction were within normal range except for absent sympathetic skin response. Targeted gene testing revealed a pathogenic homozygous loss-of-function (LOF) mutation at 5′ splice site in intron 13 of the NTRK1 gene (c.1787+1G>T) * Soumya Sundaram [email protected]; [email protected]