Congenital Insensitivity to Pain and Anhidrosis (CIPA)
Introduction[edit | edit source]
Congenital Insensitivity to Pain and Anhidrosis (CIPA) is a rare genetic disorder affecting the autonomic nervous system and is described as hereditary sensory and autonomic neuropathy type IV (HSAN IV). It is characterized by the inability to perceive pain and temperatures sensations and the inability to sweat[1]. It's incidence varies among populations but is estimated to occur in 1 in 125 million newborns[2].
Pathological Process[edit | edit source]
CIPA is a genetic disorder, inherited in an autosomal recessive pattern which means that the parents of the individual diagnosed with CIPA each carry one copy of the mutated gene and don't show symptoms or signs of the condition[3]. It is caused by mutations in neurotrophic tyrosine kinase receptor 1 ( NTRK1 ) gene. The NTRK1 gene is responsible for giving instructions for the synthesis of a receptor protein that binds to another protein called nerve growth factor beta (NGFβ). The NTRK1 is found on the surface of sensory neurons that transmit pain, temperature and touch sensations and when the NGFβ protein binds to this receptor, the process of autophosphorylation is activated which means that NTRK1 is activated and cells are signaled to grow and divide maintaining the survival of nerve cells[4]. Mutations in the NTRK1 gene lead to dysfunctions in the NGFβ protein and thus errors in transmitting signals which eventually lead to apoptosis of neuronal cells leading to inability to feel pain and temperature sensations in addition to inability to sweat due to the loss of neuronal connections to the sweat glands[5].
Reference[edit | edit source]
- ↑ Axelrod FB, Gold-von Simson G. Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet journal of rare diseases. 2007 Dec;2(1):1-2.
- ↑ Daneshjou K, Jafarieh H, Raaeskarami SR. Congenital insensitivity to pain and anhydrosis (CIPA) syndrome; a report of 4 cases. Iranian journal of pediatrics. 2012 Sep;22(3):412.
- ↑ Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditary sensory and autonomic neuropathies. Neurobiology of disease. 2006 Feb 1;21(2):247-55.
- ↑ Indo Y. Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor. Human mutation. 2001 Dec;18(6):462-71.
- ↑ Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K, Kawano T, Mitsubuchi H, Tonoki H, Awaya Y, Matsuda I. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nature genetics. 1996 Aug 1;13(4):485-8.
