What Is Muckle Wells Syndrome?

Muckle Wells Syndrome (MWS) is a rare disease that is caused by an abnormal copy of a gene. The disease affects the skin and joints of patients and also causes fever. Long term, MWS may also damage the hearing and kidneys of affected people. It is also known as Urticaria-Deafness-Amyloidosis (UDA) Syndrome. Muckle Wells Syndrome is part of a group of similar disorders called the Cryopyrin-Associated Periodic Syndromes (CAPS).

Symptoms of MWS include rashes that do not itch, joint pain, and raised temperatures. Inflamed eyes are another possible symptom. About a third of people with Muckle Wells Syndrome develop kidney damage over time due to collection of a protein called amyloid in the kidney, which is known as amyloidosis. The disease can also affect the nerves in the ear and cause deafness. Some people may also suffer from lesions on the skin.

The gene that causes the symptoms of MWS is the NLRP3 gene. Humans have two copies of each gene, usually, one set from the mother and one set from the father. Each copy of a gene codes for a particular protein, and if a gene is mutated, it can code for a protein different than normal.

NLRP3 codes for a protein called cryopyrin, and in people without the disease, the code is accurate enough for the body to make a protein that functions normally. In people with MWS, one copy, at least, of the gene is mutated, and the cryopyrin that the body makes is not normal. This mutated gene is dominant, which means that, if a person has a normal copy as well as the mutated copy, the normal copy does not prevent the disease developing.

Cryopyrin is part of the immune system's response to infection or tissue injury. It helps make up a complex of molecules called an inflammasome. The completed inflammasome acts as a signal for the body to begin the inflammation process.

The abnormal cryopyrin that people with Muckle Wells Syndrome make is much more active than usual in the inflammasome. It triggers more inflammation than necessary and causes symptoms such as fever, rash, and pain in the joints. These symptoms result from an overenthusiastic inflammatory process that damages and kills the body's own cells by accident.

Someone with MWS typically suffers recurrent episodes of inflammation over his or her lifetime. The first occurrence generally happens in childhood. Triggers for a flare-up include stress, cold, or tiredness, but sometimes there appears to be no trigger.