China
Africa
Explore chapters and articles related to this topic
Hyperkinetic Movement Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Morales-Briceno Hugo, Victor S.C. Fung, Annu Aggarwal, Philip Thompson
Leukodystrophies: Hypomyelination with basal ganglia and cerebellar atrophy syndrome (H-ABC).Pelizaeus–Merzbacher disease (PMzD).POLR3-related leukodystrophy.BCAP31 mutations.Metachromatic leukodystrophy (MLD).Krabbe's disease (KD).Xeroderma pigmentosum (XP).Aicardi–Goutières syndrome (AGS).
Aicardi Syndrome and Klinefelter Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Aicardi syndrome is unrelated to Aicardi−Goutières syndrome (AGS), which is an autosomal recessive disorder characterized by early-onset encephalopathy, intellectual and physical handicap, calcification of the basal ganglia (particularly the putamen, globus pallidus, thalamus), leukodystrophy, cerebral atrophy, chronic cerebrospinal fluid (CSF) leukocytosis, and increased concentration of interferon-alpha in the CSF. At the genetic level, AGS is linked to variations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR genes [2].
Inflammatory dermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
The clinical differential diagnoses are lichen planus, drug eruptions, id reactions, and erythema multiforme. Histologically, mainly nail lichen planus has to be excluded. Hypertrophic lupus erythematosus may mimic squamous cell carcinoma227 but elastic fiber trapping is rare in LE.228 The clinical and histopathological skin changes in the rare Aicardi-Goutières syndrome that is associated with a mutation of the TREX1 gene are identical with chilblain lupus.229
Anti-IFNαR Mabs for the treatment of systemic lupus erythematosus
Published in Expert Opinion on Biological Therapy, 2021
Bethan Goulden, David Isenberg
The IFNGS is overexpressed in 90% of children with SLE and up to 75% of adults with the disease and is higher in those with severe manifestations such as neuropsychiatric, hematological, and renal involvement [11] (though interestingly, not necessarily correlating with higher disease activity or flare [18]). Genetic polymorphisms within type 1 IFN pathways are associated with an increased risk of developing SLE. There are also a series of monogenic, inheritable disorders with SLE-like features, such as Aicardi Goutières syndrome, which are collectively known as the interferonopathies and are characterized by overproduction of type 1 IFNs [19]. Causative mutations have been identified in the metabolism of nucleic acids, nucleic acid signaling, regulatory pathways, and proteasome function. Furthermore, treatment with IFNα (for some forms of leukemia, lymphoma, carcinoid tumors, and viral hepatitis) is recognized as a potential cause of drug-induced lupus (DIL) and one of the few forms of DIL that can trigger anti-dsDNA antibody production [20]. In addition, IFNα therapy also seems capable of precipitating cases of genuine SLE with more severe and multi-system involvement than is typically seen in DIL [21]. Long before these clinical observations, accelerated disease progression in the presence of type 1 IFNs had been described in murine models of SLE [22,23].
Designation of orphan conditions in Europe: regulatory observations and considerations after implementation of regulation 141/2000
Published in Expert Opinion on Orphan Drugs, 2020
Segundo Mariz, Kerstin Westermark, Bruno Sepodes
Prevalence of a condition does not appear to be the limiting factor regarding clustering for example in Hemophilia B which has a prevalence below 1 in 10,000 (which some would call an ultra-rare condition) has 18 designations (as of the 16th of August 2019). However low Public awareness linked to low prevalence could however be associated with lower submissions and positive opinions [9]. To illustrate this point, we have highlighted some conditions which have been designated by the COMP for which few additional positive designations have occurred. Adrenoleukodystrophy a metabolic disorder with a prevalence of 0.4 in 10,000 in Europe and first designated in 2012 has had 3 more designations to date. Wolfram Syndrome another very rare metabolic condition with a prevalence in Europe estimated to be 0.2 in 10,000 had its initial designation in 2015 and only one additional designation. Aicardi-Goutieres Syndrome (prevalence reported to be 1 in 10,000) where one center in Europe has submitted two products at the same time for designation in 2015 has had no further submissions. What the limiting factor here is difficult to establish as it can be linked to factors such as limited number of centers working on the condition or limited understanding of the underlying etiology and pathophysiology or limited patient organization interaction [10]. Although a crude measure designation clustering around a new condition can offer some perception into the interest, awareness and trends regarding medicinal research and development activities associated with the specific condition considered.
Novel and emerging treatments for Aicardi-Goutières syndrome
Published in Expert Review of Clinical Immunology, 2020
Davide Tonduti, Elisa Fazzi, Raffaele Badolato, Simona Orcesi
Results were recently published from a single-center, open-label, pilot study in 8 Aicardi-Goutières syndrome patients (ClinicalTrials.gov Identifier NCT02363452) treated for 12 months with a combination of three RTIs (abacavir, lamivudine, and zidovudine). This is the first such study in AGS. Only patients with mutations in the TREX1, RNASEH2A, RNASEH2B, RNASEH2C or SAMHD1 genes were included. The study demonstrated a reduction in IFN signaling without evidence of side effects in 8 patients with mutations in TREX1, RNASEH2A, RNASEH2B and SAMHD1. From a clinical perspective, no changes were observed, but the authors declared that the recruited patients were already in an advanced stage of the disease and presented severe disability, therefore clinical improvements had not been expected and did not constitute an aim of this pilot study. In three patients MRI showed a possible augmentation of resting cerebral blood flow, but larger groups of patients are needed to verify a possible correlation with RTI treatment [12].