CMT2C Patient Experienced Heat Surges and Inability to Sweat, Case Study Reports

A woman with Charcot–Marie–Tooth disease was unable to regulate her body temperature, experiencing heat surges and an inability to sweat, according to a Canadian case study.

Researchers said they were unable to find another report of this problem. It likely stems from the TRPV4 gene mutation the patient had, they said. She had the type 2c version of CMT, they said.

The case study, “Case of Charcot–Marie–Tooth Type 2C Due to a TRPV4 Gene Mutation With Isolated Sudomotor Autonomic Dysfunction,” appeared in the Journal of Clinical Neuromuscular Disease.

CMT2 patients have nerve damage that affects axons, the long fibers connecting nerve cells with other cells or muscles.

The cause of CMT2C is mutations of the TRPV4 gene, scientists say. Hallmarks of the condition include weakness in the limbs; the diaphragm, which controls breathing; and the muscles of the larynx, or voice box. Another characteristic is vocal cord paralysis.

In addition, patients may have difficulty breathing, a hoarse voice, and a high-pitched breathing sound known as stridor.

The first CRT-related symptom that the 57-year-old woman displayed was partial vocal cord paralysis stemming from the disruption of nerve impulses in the larynx. Previous breathing difficulties had led to her having a tracheostomy — surgery that created a hole in her windpipe to give her an alternative way to breathe.

But her main complaint was body temperature fluctuations. She had frequent surges of heat and was unable to sweat normally, managing the problems with water and ice packs.

Doctors tested her autonomic function, which covers breathing, sweating, digestion, and heartbeat. They discovered significant sweat gland dysfunction in her forearms, legs and feet.

Her heart rate and blood pressure were satisfactory, however.

The team searched online medical databases for information about her condition. They found no report of a CMT2C patient with a TRPV4 mutation experiencing temperature regulation and sweat gland dysfunction.

The gene provides instructions for making a protein that acts as a calcium channel. TRPV4 mutations lead to too much calcium flowing into cells. One result is nervous system problems.

TRPV4 channels cover several parts of the body, including the nervous system, kidneys, inner ear, and skin.

Studies in rodents have shown that TRPV4 ion channels help regulate temperatures in both the central nervous system, which includes the brain and spinal cord, and the peripheral nervous system, which covers other areas of the body.

When over-activated, the ion channels can cause body temperatures to drop. When blocked, they can cause temperatures to rise.

“Together, these data support a central and peripheral [nervous system] role for TRPV4 channels in autonomic temperature regulation that may be interrupted in persons with a TRPV4 mutation,” the researchers wrote.

The team said their discovery that a CMT2C patient had temperature-regulation and sweat-production problems was important because it added to the list of symptoms doctors could look for in these patients.