The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Michio Hirano - One of the best experts on this subject based on the ideXlab platform.

  • alpha 1 antitrypsin promoter improves the efficacy of an adeno associated virus vector for the treatment of mitochondrial neurogastrointestinal Encephalomyopathy
    Human Gene Therapy, 2019
    Co-Authors: Michio Hirano, Ramon Martí, Raquel Cabreraperez, Ferran Vilajulia, Federico Mingozzi, Javier Torrestorronteras
    Abstract:

    Mitochondrial neurogastrointestinal Encephalomyopathy (MNGIE) is a devastating disease caused by mutations in TYMP, which encodes thymidine phosphorylase (TP). In MNGIE patients, TP dysfunction res...

  • long term sustained effect of liver targeted adeno associated virus gene therapy for mitochondrial neurogastrointestinal Encephalomyopathy
    Human Gene Therapy, 2017
    Co-Authors: Javier Torrestorronteras, Michio Hirano, Raquel Cabreraperez, Ferran Vilajulia, Carlo Viscomi, Yolanda Camara, Massimo Zeviani
    Abstract:

    Mitochondrial neurogastrointestinal Encephalomyopathy (MNGIE) is caused by mutations in TYMP, the gene encoding the enzyme thymidine phosphorylase (TP). TP dysfunction results in systemic accumulat...

  • Thymidine phosphorylase is both a therapeutic and a suicide gene in a murine model of mitochondrial neurogastrointestinal Encephalomyopathy
    Gene Therapy, 2014
    Co-Authors: Sergio Lopez-estevez, Javier Torres-torronteras, María José Mansilla, Silvia Casacuberta-serra, Lluís Martorell, G Ferrer, Michio Hirano, Ramon Martí, Jordi Barquinero
    Abstract:

    Thymidine phosphorylase is both a therapeutic and a suicide gene in a murine model of mitochondrial neurogastrointestinal Encephalomyopathy

  • Clinical and genetic spectrum of mitochondrial neurogastrointestinal Encephalomyopathy
    Brain, 2011
    Co-Authors: Caterina Garone, Saba Tadesse, Michio Hirano
    Abstract:

    Mitochondrial neurogastrointestinal Encephalomyopathy is a rare multisystemic autosomic recessive disorder characterized by: onset typically before the age of 30 years; ptosis; progressive external ophthalmoplegia; gastrointestinal dysmotility; cachexia; peripheral neuropathy; and leucoencephalopathy. The disease is caused by mutations in the TYMP gene encoding thymidine phosphorylasethymine phosphorylase. Anecdotal reports suggest that allogeneic haematopoetic stem cell transplantation may be beneficial for mitochondrial neurogastrointestinal Encephalomyopathy, but is associated with a high mortality. After selecting patients who fulfilled the clinical criteria for mitochondrial neurogastrointestinal Encephalomyopathy and had severe thymidine phosphorylase deficiency in the buffy coat ( G in Europe and c.518T>G in the Dominican Republic, that could guide genetic screening in each location. Although the sequence of clinical manifestations in the disease varied, half of the patients initially had gastrointestinal symptoms. We confirmed anecdotal reports of intra- and inter-familial clinical variability and absence of genotype–phenotype correlation in the disease, suggesting genetic modifiers, environmental factors or both contribute to disease manifestations. Acute medical events such as infections often provoked worsening of symptoms, suggesting that careful monitoring and early treatment of intercurrent illnesses may be beneficial. We observed endocrine/exocrine pancreatic insufficiency, which had not previously been reported. Kaplan–Meier analysis revealed significant mortality between the ages of 20 and 40 years due to infectious or metabolic complications. Despite increasing awareness of this illness, a high proportion of patients had been misdiagnosed. Early and accurate diagnosis of mitochondrial neurogastrointestinal Encephalomyopathy, together with timely treatment of acute intercurrent illnesses, may retard disease progression and increase the number of patients eligible for allogeneic haematopoetic stem cell transplantation.

  • infantile Encephalomyopathy and nephropathy with coq10 deficiency a coq10 responsive condition
    Neurology, 2005
    Co-Authors: Leonardo Salviati, S Sacconi, Luisa Murer, G Zacchello, L Franceschini, A M Laverda, Giuseppe Basso, Catarina M Quinzii, C Angelini, Michio Hirano
    Abstract:

    Coenzyme Q10 (CoQ10) deficiency has been associated with various clinical phenotypes, including an infantile multisystem disorder. The authors report a 33-month-old boy who presented with corticosteroid-resistant nephrotic syndrome in whom progressive Encephalomyopathy later developed. CoQ10 was decreased both in muscle and in fibroblasts. Oral CoQ10 improved the neurologic picture but not the renal dysfunction.

Ramon Martí - One of the best experts on this subject based on the ideXlab platform.

Massimiliano Filosto - One of the best experts on this subject based on the ideXlab platform.

  • Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)
    MDPI AG, 2018
    Co-Authors: Massimiliano Filosto, Stefano Cotti Piccinelli, Filomena Caria, Serena Gallo Cassarino, Enrico Baldelli, Anna Galvagni, Irene Volonghi, Mauro Scarpelli, Alessandro Padovani
    Abstract:

    Mitochondrial neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause a loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues, and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Other two MNGIE-type phenotypes have been described so far, which are linked to mutations in POLG and RRM2B genes. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped thymidine phosphorylase therapy) and newer, promising therapies are expected in the near future. Since successful treatment is strictly related to early diagnosis, it is essential that clinicians be warned about the clinical features and diagnostic procedures useful to suspect diagnosis of MNGIE-MTDPS1. The aim of this review is to promote the knowledge of the disease as well as the involved mechanisms and the diagnostic processes in order to reach an early diagnosis

  • Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal Encephalomyopathy
    Brain, 2015
    Co-Authors: Joerg Halter, W Michael, Michael Schupbach, Hanna Mandel, Carlo Casali, Matthew Collin, David Valcarcel, Attilio Rovelli, Kim H. Orchard, Massimiliano Filosto
    Abstract:

    Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal Encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal Encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal Encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus

  • pitfalls in diagnosing mitochondrial neurogastrointestinal Encephalomyopathy
    Journal of Inherited Metabolic Disease, 2011
    Co-Authors: Massimiliano Filosto, Mauro Scarpelli, Paola Tonin, Silvia Testi, Maria Cotelli, Mara Rossi, Andrea Salvi, Alberto Grottolo, Valentina Vielmi, Alice Todeschini
    Abstract:

    Mitochondrial neurogastrointestinal Encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic options (peritoneal dialysis, allogeneic stem cell transplantation, enzyme replacement) makes it necessary to diagnose the disease early, which is not always achieved due to the difficulty in recognizing this disorder, especially in case of atypical presentation. We describe three MNGIE patients with atypical onset of the disease. In the first patient the main symptoms were long-standing chronic fever, recurrent acute migrant arthritis, and gastrointestinal disorders mimicking autoimmune or inflammatory intestinal diseases; the second patient complained only of exercise intolerance and muscle cramps, and the third patient had a CIDP-like polyneuropathy. This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies.

Raquel Cabreraperez - One of the best experts on this subject based on the ideXlab platform.

Ferran Vilajulia - One of the best experts on this subject based on the ideXlab platform.