CIPA Disease: When a Person Can't Feel Pain

Congenital insensitivity to pain and anhydrosis (CIPA) is a rare hereditary disease that causes affected individuals to be unable to feel pain and unable to sweat (anhydrosis). It is also called hereditary sensory and autonomic neuropathy type IV (HSAN IV).

This name is very descriptive because it defines several important characteristics of the disease.

The condition is hereditary, meaning that it runs in families. Sensory neuropathy means that it is a nerve disease that specifically affects the nerves that control sensation. Autonomic nerves are the nerves that control survival functions of the body. CIPA, or HSAN IV, specifically affects the autonomic nerves that control sweat.

Symptoms of CIPA

CIPA disease is present at birth and makes people unable to sense pain or temperature and unable to sweat. The symptoms become apparent during childhood and the disease is typically diagnosed during childhood.

Lack of Pain: Most people who have CIPA do not complain of 'lack of pain' or 'lack of sweat.' Instead, children with CIPA initially experience injuries or burns without crying, complaining or even noticing. Parents may observe that a child with CIPA is just a mild-mannered kid, rather than noticing a problem. After a while, parents might begin to wonder why the child doesn't respond to pain, and the child’s doctor would likely run some diagnostic tests for nerve disease.

Children with CIPA typically become repeatedly injured or burned because they do not avoid painful activity. And, they can even develop infected wounds because they do not instinctively protect their wounds from further pain. Sometimes, children with CIPA need to be medically evaluated for excessive injuries.

When the medical team observes unusually calm behavior in the face of pain, this can prompt an evaluation for sensory neuropathy.

Anhydrosis (Lack of Sweating): Hydrosis means sweating. Anhydrosis means lack of sweating. Normally, sweat on the surface of the skin helps cool off the body when we get too hot from exercise or from a high fever. Children (and adults) with CIPA suffer consequences of anhydrosis, such as excessively high fevers, because they lack the ‘cooling off’ protection that sweating can provide.

Diagnosis

There are not simple X-ray tests or blood tests that can identify CIPA. Some people who have CIPA have abnormally underdeveloped nerves and a lack of sweat glands on a biopsy.

The most definitive diagnostic test for CIPA is a genetic test, which can be done before birth or during childhood or adulthood. There is a known genetic abnormality that identifies CIPA, and it is called the human TRKA (NTRKI) gene located on chromosome 1 (1q21-q22). A genetic DNA test can identify an abnormality of this gene, confirming the diagnosis of CIPA.

Primary Causes

CIPA is a hereditary disease. It is autosomal recessive, which means that any person who has CIPA must inherit the gene from both parents.

Typically, the parents of an affected child carry the gene, but do not have the disease if they only inherited the gene from one parent.

The abnormal gene responsible for CIPA, human TRKA (NTRK1), is a gene that directs the body to develop mature nerves. It specifically promotes nerve growth by encoding a receptor called tyrosine kinase (RTK,), which is autophosphorylated in response to nerve growth factor (NGF).

When this gene is defective, as it is among those who have CIPA, the sensory nerves and some autonomic nerves do not fully develop, and thus the sensory nerves cannot function properly to sense messages of pain and temperature and the body cannot produce sweat.

Treatment for CIPA

At the current time, there is no available treatment that can cure CIPA disease or replace the missing sensation of pain or the function of sweating.

Children with the disease have to learn to try to prevent injuries and to monitor injuries carefully in order to avoid infection. Parents and other adults who care for children with CIPA must also remain vigilant, as children naturally may want to try new things without fully understanding the potential significance of physical injuries.

Expectations

If you or a loved one has been diagnosed with CIPA, you can have a healthy and productive life with good medical care and lifestyle adjustments. Knowing that it is a genetic disease is an important consideration when it comes to family planning.

CIPA is a rare disorder, and often, finding support groups for unique health problems can help in terms of gaining social support and learning about practical tips to help make living with CIPA easier.

Sources:

A Comprehensive Functional Analysis of NTRK1 Missense Mutations Causing Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV), Shaikh SS, Chen YC, Halsall SA, Nahorski MS, Omoto K, Young GT, Phelan A, Woods CG, Hum Mutat. 2017 Jan;38(1):55-63

Mutations in TrkA Causing Congenital Insensitivity to Pain with Anhidrosis (CIPA) Induce Misfolding, Aggregation, and Mutation-dependent Neurodegeneration by Dysfunction of the Autophagic Flux. Franco ML, Melero C, Sarasola E, Acebo P, Luque A, Calatayud-Baselga I, García-Barcina M, Vilar M, J Biol Chem. 2016 Oct 7;291(41