An increased amount of N-acetylaspartic acid was found in urine and plasma of three patients, from two families, with the diagnosis of cerebral spongy degeneration (Canavan disease). Aspartoacylase was assayed in cultured skin fibroblasts from one patient of each family and a profound deficiency of this enzyme was found. Although the function of N-acetylaspartic acid is not understood, it is known to occur in high concentration in human brain. The finding of a defect in the metabolism of N-acetylaspartic acid causing progressive spongy degeneration of the brain may lead to a better understanding of the function of this amino acid derivative. The aspartoacylase assay affords a new tool for determining the diagnosis of Canavan disease. Since aspartoacylase activity was present in cultured amniotic cells and chorionic villi, it is likely that the assay for this enzyme can be used for the prenatal diagnosis of Canavan disease.

BackgroundFibromyalgia (FM) is a clinical syndrome characterized by chronic pain and allodynia. The diagnosis of FM has been one of exclusion as a test to confirm the diagnosis is lacking. Recent data highlight the role of the immune system in FM. Aberrant expressions of immune mediators, such as cytokines, have been linked to the pathogenesis and traits of FM. We therefore determined whether cytokine production by immune cells is altered in FM patients by comparing the cellular responses to mitogenic activators of stimulated blood mononuclear cells of a large number of patients with FM to those of healthy matched individuals.MethodsPlasma and peripheral blood mononuclear cells (PBMC) were collected from 110 patients with the clinical diagnosis of FM and 91 healthy donors. Parallel samples of PBMC were cultured overnight in medium alone or in the presence of mitogenic activators; PHA or PMA in combination with ionomycin. The cytokine concentrations of IFN-γ, IL-5, IL-6, IL-8, IL-10, MIP-1β , MCP-1, and MIP1-α in plasma as well as in cultured supernatants were determined using a multiplex immunoassay using bead array technology.ResultsCytokine levels of stimulated PBMC cultures of healthy control subjects were significantly increased as compared to matched non-stimulated PBMC cultures. In contrast, the concentrations of most cytokines were lower in stimulated samples from patients with FM compared to controls. The decreases of cytokine concentrations in patients samples ranged from 1.5-fold for MIP-1β to 10.2-fold for IL-6 in PHA challenges. In PMA challenges, we observed 1.8 to 4-fold decreases in the concentrations of cytokines in patient samples.ConclusionThe cytokine responses to mitogenic activators of PBMC isolated from patients with FM were significantly lower than those of healthy individuals, implying that cell-mediated immunity is impaired in FM patients. This novel cytokine assay reveals unique and valuable immunologic traits, which, when combined with clinical patterns, can offer a diagnostic methodology in FM.

No abstract

No abstract

No abstract