Name: Proteasome-associated autoinflammatory syndrome-5 | Acronym: PRAAS5
Alt. names: CANDLE

Gene: PSMB10 | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 0 | First reported in: 2020

Last updated on: 2024-11-09 17:21:13 by Xiao P. Peng

OMIM: 619175

Orphanet: -

MONDO: -

DOID: -

ClinGen:

PRAAS is characterized by early-onset recurrent fevers, periorbital erythema and swelling, skin lesions (panniculitis with evidence of neutrophilic dermatosis on biopsy), and lipodystrophy, in addition to intra- and/or extra-cranial calcinosis, myositis, lymphadenopathy, hepatosplenomegaly, progressive joint contractures, metabolic syndrome, recurrent infections and multi-organ failure. Patients may be triggered by acute stressors such as cold, physical stress, or infections, leading to a vicious feed-forward cycle of inflammatory chemokine and cytokine production by both hematopoietic and nonhematopoietic cells that may affect any organ. Immunophenotyping may be unremarkable or show overt lymphocyte subset abnormalities and patients can have nonspecifically elevated inflammatory markers, cytopenias, transaminitis, dyslipidemia, hypergammaglobulinemia and variable autoantibody production, along with increased type I IFN production and strong peripheral blood ISGs. Sarrabay et al. (2020) reported a 3-year-old girl, born of consanguineous Algerian parents, with PRAAS-type autoinflammation. She presented on day 7 of life with a recurrent polymorphic disseminated cutaneous rash that had annular lesions. Cutaneous biopsy showed nonspecific lymphocytic infiltration. She also had fever, failure to thrive, persistent hepatosplenomegaly, emaciated face, and long slender fingers. Laboratory studies showed elevated acute-phase reactants and microcytic anemia in the context of a minor thalassemia trait. There was a partial response to steroid and methotrexate treatment, but she relapsed when doses were reduced. In addition to type I IFN activation, she also showed elevated levels of TNF-α and IL-6 but not IL-18 or IL-1β (PMID: 31783057).

JAK inhibitors have been shown to ameliorate disease activity (PMID: 29649002), while HSCT can be curative (PMID: 34416217, 34131834, 33727065).