Proteasome-Associated Autoinflammatory Syndrome 6, (PRAAS6)
OMIM number: 620796
Comments closing date: 10/07/2026
Proteasome-Associated Autoinflammatory Syndrome 6 (PRAAS6) is an extremely rare, inherited disorder that causes the immune system to attack the body's own tissues, resulting in severe, chronic inflammation starting in early infancy with high level or mortality. It is a type of proteasomopathy meaning it is caused by a malfunction in the proteasome, the cellular machinery responsible for breaking down and recycling damaged or unnecessary proteins.
Recurrent Fevers: Persistent high temperatures, often starting in the first months of life. Skin
Rashes/Lesions: Inflammatory skin changes, sometimes appearing as red, swollen nodules or
patches. Lipodystrophy: Progressive loss of subcutaneous fat, often starting in the face and
upper body. Muscle and Joint Involvement: Weakness (myositis) and stiffness (contractures).
Organ Dysfunction: Enlargement of the liver and spleen (hepatosplenomegaly), liver issues,
pulmonary hypertension, and brain calcifications. Immunodeficiency: Despite the high inflammation,
patients may also have a weakened immune system against infections. Management: There is
no cure. Treatment often focuses on managing inflammation. Recent research indicates that JAK
inhibitors (such as baricitinib) may be effective in reducing the inflammation and improving symptoms by blocking the pathways activated by the faulty proteasome. Stem cell transplantation has resulted in no disease recurrence.
