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Background and purpose: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non‐coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. Methods: MiR‐146a, miR‐155 and miR‐132 were quantified by real‐time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2–ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. Results: Serum levels of miR‐146a and miR‐155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR‐146a, miR‐155 and miR‐132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. Conclusions: Our results indicate that miR‐146a, miR‐155 and miR‐132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a rare monogenic autoinflammatory disease. Its most severe manifestation is secondary amyloidosis. A 44-year-old male presented with nephrotic syndrome. Kidney biopsy was conclusive for secondary amyloidosis. The patient and his children had a history of recurrent febrile periods since infancy. All subjects were positive for a heterozygous variant of the TNFRSF1A gene, confirming TRAPS diagnosis. The patient progressed to end-stage renal failure and developed recurrent pericarditis episodes. He was started on anakinra while on hemodialysis with marked reduction of his serum amyloid A protein (SAA) levels. Meanwhile he received a cadaveric renal transplant and maintains anakinra treatment. Despite renal failure being the most feared complication of AA amyloidosis caused by TRAPS, little data is available about safety of anti-IL-1 treatment in patients with severe kidney failure. The authors report this case of a patient on dialysis treated with anakinra in which no complications were registered. Though amyloidosis is established, the authors believe containing its progression and reducing inflammatory activity can improve patient prognosis and reduce recurrence of amyloidosis in kidney transplant, as has been demonstrated in transplanted patients due to familial Mediterranean fever amyloidosis. [ABSTRACT FROM AUTHOR]

We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder with a homogeneous presentation: progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and subcortical leukoencephalopathy. Increased levels of L-2-hydroxyglutaric acid in body fluids proved the diagnosis of L-2-HGA in all 21 patients. We analyzed the L-2-HGA gene (L2HGDH), recently found to be mutated in consanguineous families with L-2-HGA, and identified seven novel mutations in 15 families. Three mutations appeared to be particularly prevalent in this Portuguese panel: a frameshift mutation (c.529delC) was detected in 12 out of 30 mutant alleles (40%), a nonsense mutation (c.208C>T; p.Arg70X) in 7/30 alleles (23%), and a missense mutation (c.293A>G; p.His98Arg) in four out of 30 mutant alleles (13%), suggesting that common origin may exist. Furthermore, two novel missense (c.169G>A; p.Gly57Arg, c.1301A>C; p.His434Pro) and two splice error (c.257-2A>G, c.907-2A>G) mutations were found. All the mutations presumably lead to loss-of-function with no relationship between clinical signs, progression of the disease, levels of L-2-HGA and site of the mutation. In the three remaining families, no pathogenic mutations in the L-2-HGA were found, which suggests either alterations in regulatory regions of the gene or of its intervening sequences, compound heterozygosity for large genomic deletion and, or further genetic heterogeneity. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]