Muckle-Wells syndrome
Encyclopedia
Muckle–Wells syndrome also known as (UDA), is a rare
autosomal dominant disease which causes sensorineural
deafness, recurrent hives
, and can lead to amyloidosis
. Individuals with MWS often have episodic fever, chills, and painful joint
s. As a result, MWS is considered a type of periodic fever syndrome
. MWS is caused by a defect in the CIAS1
gene which creates the protein cryopyrin. MWS is closely related to two other syndromes, familial cold urticaria
and neonatal onset multisystem inflammatory disease
— in fact, all three are related to mutations in the same gene and subsumed under the term cryopyrin-associated periodic syndrome
s (CAPS).
gene leads to increased activity of the protein cryopyrin. This protein is partly responsible for the body's response to damage or infection. During these states, a chemical called interleukin 1β
is produced by an immune cell
known as a macrophage
. This chemical interacts with a receptor
on the surface of other immune cells to produce symptoms of inflammation
such as fever, arthritis
, and malaise. In MWS, the increased activity of cryopyrin leads to an increase in interleukin 1β. This leads to inflammation all throughout the body with the associated symptoms.
s in the kidney, a condition known as amyloidosis.
In an episode of TV series Cake Boss, Buddy Valastro works with a girl with this condition through Make-A-Wish Foundation.
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
autosomal dominant disease which causes sensorineural
Sensorineural hearing loss
Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
deafness, recurrent hives
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, and can lead to amyloidosis
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
. Individuals with MWS often have episodic fever, chills, and painful joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s. As a result, MWS is considered a type of periodic fever syndrome
Periodic fever syndrome
The periodic fever syndromes are a set of disorders, many of which are genetic disorders in which the mechanisms which initiate and control inflammation are disturbed, leading to uncontrolled inflammation throughout the body...
. MWS is caused by a defect in the CIAS1
CIAS1
NACHT, LRR and PYD domains-containing protein 3 or cryopyrin is a protein that in humans is encoded by the NLRP3 gene. The gene is also called cold induced autoinflammatory syndrome 1 and is located on the long arm of chromosome 1...
gene which creates the protein cryopyrin. MWS is closely related to two other syndromes, familial cold urticaria
Familial cold urticaria
Familial cold urticaria is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22°C .It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells...
and neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease
Neonatal onset multisystem inflammatory disease is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period...
— in fact, all three are related to mutations in the same gene and subsumed under the term cryopyrin-associated periodic syndrome
Cryopyrin-associated periodic syndrome
Cryopyrin-associated periodic syndrome is a spectrum of autoinflammatory syndromes including familial cold autoinflammatory syndrome , the Muckle-Wells syndrome , and neonatal-onset multisystem inflammatory disease...
s (CAPS).
Sign and symptoms
- SensorineuralSensorineural hearing lossSensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
deafness - Recurrent urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
(hives) - Fevers
- Chills
- ArthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
(painful joints)
Possible causes
MWS occurs when a mutation in the CIAS1CIAS1
NACHT, LRR and PYD domains-containing protein 3 or cryopyrin is a protein that in humans is encoded by the NLRP3 gene. The gene is also called cold induced autoinflammatory syndrome 1 and is located on the long arm of chromosome 1...
gene leads to increased activity of the protein cryopyrin. This protein is partly responsible for the body's response to damage or infection. During these states, a chemical called interleukin 1β
IL1B
Interleukin-1 beta also known as catabolin, is a cytokine protein that in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β.- Function :Interleukin 1 was discovered by Gery in 1972...
is produced by an immune cell
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
known as a macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
. This chemical interacts with a receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
on the surface of other immune cells to produce symptoms of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
such as fever, arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, and malaise. In MWS, the increased activity of cryopyrin leads to an increase in interleukin 1β. This leads to inflammation all throughout the body with the associated symptoms.
Treatment
- Treatment with anakinraAnakinraAnakinra is a drug used to treat rheumatoid arthritis.-Mechanism:Anakinra is an interleukin-1 receptor antagonist...
, an interleukin 1 receptor antagonist, can lead to an improvement in the hearing loss. - RilonaceptRilonaceptRilonacept also known as IL-1 Trap , is a dimeric fusion protein consisting of the extracellular domain of human interleukin-1 receptor and the FC domain of human IgG1 that binds and neutralizes IL-1.Rilonacept is used for the treatment of cryopyrin-associated periodic syndromes , including familial...
(Arcalyst) a dimeric fusion protein for the treatment of CAPS. - CanakinumabCanakinumabCanakinumab is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha....
, a monoclonal antibody against interleukin-1β
Prognosis
The chronic inflammation present in MWS over time can lead to deafness. In addition, the prolonged inflammation can lead to deposition of proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s in the kidney, a condition known as amyloidosis.
Pop culture
In the episode of popular TV series House, the main patient of the Season 7 episode "Recession Proof" is ultimately diagnosed with this condition.In an episode of TV series Cake Boss, Buddy Valastro works with a girl with this condition through Make-A-Wish Foundation.
See also
- Familial cold urticariaFamilial cold urticariaFamilial cold urticaria is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22°C .It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells...
, a similar disease - List of cutaneous conditions
- NOMID, a similar disease
- Urticarial syndromesUrticarial syndromesThere are several distinct Urticarial syndromes including:* Muckle–Wells syndrome* Familial Mediterranean fever* Systemic capillary leak syndrome...
External links
- NOMID Alliance, a non-profit charity devoted to CAPS diseases
- Muckle-Wells Syndrome Community on RareShare