Proteasome-associated autoinflammatory syndrome

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ORPHA:324977OMIM:619175D89.8
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Overview

Proteasome-associated autoinflammatory syndrome (PRAAS), also known as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome), Nakajo-Nishimura syndrome (NNS), or joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome), is a group of rare genetic conditions caused by problems with the proteasome — a tiny machine inside your cells that breaks down damaged or unneeded proteins. When the proteasome doesn't work properly, damaged proteins build up and trigger constant, uncontrolled inflammation throughout the body. People with PRAAS typically develop symptoms in early childhood, including recurring fevers that don't respond to antibiotics, skin rashes (often ring-shaped, red-violet lesions), progressive loss of body fat (lipodystrophy), joint contractures (stiffness that limits movement), muscle wasting, and swollen eyelids. Over time, the ongoing inflammation can damage multiple organs, including the liver, lungs, and brain. Blood tests often show signs of chronic inflammation, anemia, and elevated liver enzymes. Treatment focuses on controlling the overactive immune response. JAK inhibitors, particularly baricitinib, have shown significant benefit in many patients by blocking the inflammatory signals driven by interferon. However, there is currently no cure, and patients typically require lifelong treatment. Corticosteroids and other immunosuppressive drugs may also be used but often provide only partial relief. Early diagnosis and treatment are important to prevent organ damage and improve quality of life.

Also known as:

Key symptoms:

Recurring fevers starting in infancy or early childhoodRed-violet skin rashes or nodulesProgressive loss of body fat, especially in the face and armsSwollen or puffy eyelidsJoint stiffness and contracturesMuscle wasting and weaknessEnlarged liver or spleenAnemia (low red blood cell count)Delayed growth and short statureSwollen fingers and toesCalcium deposits in the brain (brain calcifications)Chronic fatigueElevated inflammatory markers in blood testsSkin thickening or hardening

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Proteasome-associated autoinflammatory syndrome.

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No actively recruiting trials found for Proteasome-associated autoinflammatory syndrome at this time.

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No specialists are currently listed for Proteasome-associated autoinflammatory syndrome.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Proteasome-associated autoinflammatory syndrome.

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Community

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Caregiver Resources

NORD Caregiver Resources

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Mental Health Support

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Family & Caregiver Grants

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Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.Which specific gene mutation is causing my (or my child's) condition, and does this affect treatment options?,Is baricitinib or another JAK inhibitor appropriate, and how do we access it?,What monitoring and blood tests will be needed, and how often?,What are the signs that the disease is getting worse or that treatment needs to be adjusted?,Are there clinical trials currently enrolling for PRAAS that we should consider?,What specialists should be part of our care team, and how often should we see them?,What can we do at home to manage symptoms and maintain quality of life?

Common questions about Proteasome-associated autoinflammatory syndrome

What is Proteasome-associated autoinflammatory syndrome?

Proteasome-associated autoinflammatory syndrome (PRAAS), also known as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome), Nakajo-Nishimura syndrome (NNS), or joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome), is a group of rare genetic conditions caused by problems with the proteasome — a tiny machine inside your cells that breaks down damaged or unneeded proteins. When the proteasome doesn't work properly, damaged proteins build up and trigger constant, uncontrolled inflammation t

How is Proteasome-associated autoinflammatory syndrome inherited?

Proteasome-associated autoinflammatory syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Proteasome-associated autoinflammatory syndrome typically begin?

Typical onset of Proteasome-associated autoinflammatory syndrome is infantile. Age of onset can vary across affected individuals.