Dysregulation of the inflammasome is associated with the onset and progression of several autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic fever syndrome, familial Mediterranean fever, rheumatoid arthritis, and systemic lupus erythematosus.
The delay in diagnosis of these four common diseases (familial Mediterranean fever, cryopyrin-associated periodic fever syndrome, mevalonate kinase deficiency, and TNF receptor-associated periodic fever syndrome) results in secondary amyloidosis of the kidney.
The NLRP3 inflammasome is associated with the onset and progression of autoinflammatory and autoimmune diseases, including metabolic disorders, multiple sclerosis, inflammatory bowel disease, and cryopyrin-associated periodic fever syndrome.
Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated periodic syndrome (CAPS).
Additionally, constitutive IL-1β secretion from LPS-primed PBMCs of cryopyrin-associated periodic fever syndromes patients was substantially reduced by high doses of PGE2.
Deficiency of MVK is associated with two rare periodic fever syndromes, mevalonic aciduria (MA), a severe form and hyper-immunoglobulin-D syndrome (HIDS), a milder form.
One patient with HIDS and FMF presented with atypical overlapping PFS clinical manifestations and genetic evaluation showed a unique combination of p.I268T/p.V377IMVK mutations and p.E230K/-MEFV variant.
Defects in mevalonate kinase, a critical rate-limiting enzyme in cholesterol and isoprene metabolism, have been associated with 2 clinical phenotypes: mevalonic aciduria, which presents in infancy or early childhood with growth failure, dysmorphic features, and neurologic disease; and hyperimmunoglobulinemia D and periodic fever syndrome, which usually presents outside the neonatal period as an autoinflammatory periodic fever syndrome.
This review summarizes the clinical manifestations, genetic analysis and therapy of FMF, TNF-alpha receptor-associated periodic fever syndrome, hyperimmunoglobulinaemia D periodic fever syndrome and cryopyrin-associated periodic fever syndrome.
Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa.
Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-igd and periodic fever syndrome: its application as a diagnostic tool.
Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.