Name of disease:

ICD-10 diagnosis code:

Causes:

• The NTRK1 gene provides instructions for making a receptor protein that attaches to another protein called NGFβ.
• The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons).
• When the NGFβ protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive.
• Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signalling, neurons die by a process of self-destruction called apoptosis.
• Loss of sensory neurons leads to the inability to feel pain in people with CIPA.
• People with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.

Mode of inheritance:

• CIPA is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Prevalence:

Diagnosis:

Age of onset:

Common signs and symptoms:

• Inability to feel pain and temperature
  - Unintentional self-injury, typically by biting the tongue, lips, or fingers, may lead to spontaneous amputation of the affected area.
  - People with CIPA heal slowly from skin and bone injuries.
  - Repeated trauma can lead to chronic bone infections (osteomyelitis) or Charcot joints, in which the bones and tissue surrounding joints are destroyed.

• Decreased or absent sweating (anhidrosis)
• Thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails
• Patches on scalp where hair does not grow (hypotrichosis)
• Hyperactivity or emotional instability
• Weak muscle tone (hypotonia)

Available treatment (medicinal and non-medicinal):

• No consensus on treatment or surveillance guidelines has been developed.
• Treatment is supportive based, which mainly focuses on regular visits with a doctor to receive a full workup to be sure that they do not have any insensitive internal problems that can be fatal.
• In addition, opioid-antagonist naloxone has shown promising results in treatments reversing the analgesia.

Disease management tips:

• Prevent injuries, e.g., installing soft-round edging on tables and protruding objects, guarding all heating devices, providing close supervision of younger children in the kitchen, and avoiding jumping, high-impact/contact sports, pastimes, and jobs that involve the potential for blunt injury or severe bone and joint trauma.
• Avoid hot or cold environments, hot or cold foods, hot showers or baths, heating blankets, particularly in the perioperative period.
• Monitor body temperature to enable timely treatment of hyper- or hypothermia.

References:

Other useful websites: