4 results on '"Bedoyan, Jirair K."'
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2. Early prediction of phenotypic severity in Citrullinemia Type 1
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Zielonka, Matthias, Kölker, Stefan, Gleich, Florian, Stützenberger, Nicolas, Nagamani, Sandesh C S, Gropman, Andrea L, Hoffmann, Georg F, Garbade, Sven F, Posset, Roland, Sarajlija, Adrijan, Skouma, Anastasia, Schulze, Andreas, Garcia‐Cazorla, Angeles, Lund, A M, Jalan, Anil, Morris, Andrew, Dionisi‐Vici, Carlo, De Laet, Corinne, Leão Teles, Elisa, Diaz, G A, Berry, G T, Payan‐Walters, Irma, Blasco‐Alonso, Javier, Seminara, Jennifer, Bedoyan, Jirair K, Merritt, J Lawrence, Burrage, Lindsay C, Yudkoff, Marc, Schiff, Manuel, Baumgartner, Matthias R, et al, University of Zurich, and Posset, Roland
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2728 Neurology (clinical) ,10036 Medical Clinic ,2800 General Neuroscience ,610 Medicine & health - Published
- 2019
3. Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders
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Posset, Roland, Gropman, Andrea L., Nagamani, Sandesh C. S., Burrage, Lindsay C., Bedoyan, Jirair K., Wong, Derek, Berry, Gerard T., Baumgartner, Matthias R., Yudkoff, Marc, Zielonka, Matthias, Hoffmann, Georg F., Burgard, Peter, Schulze, Andreas, McCandless, Shawn E., Garcia‐Cazorla, Angeles, Seminara, Jennifer, Garbade, Sven F., Kölker, Stefan, Lee, Brendan, Harding, Cary O., Coughlin, Curtis R., Le Mons, Cynthia, Dobbelaere, Dries, Leão Teles, Elisa, Cortès‐Saladelafont, Elisenda, Gleich, Florian, Eyskens, Francois, Enns, Gregory, Wilkening, Greta N., Barić, Ivo, Lawrence Merritt, J., Heringer, Jana, Blasco‐Alonso, Javier, Zeman, Jiri, Häberle, Johannes, Sykut‐Cegielska, Jolanta, Djordjevic, Maja, Batshaw, Mark L., Summar, Marshall, Freisinger, Peter, Gallagher, Renata C., Berry, Susan A., Waisbren, Susan, Stricker, Tamar, and for the Urea Cycle Disorders Consortium and the European Registry and Network for Intoxication Type Metabolic Diseases Consortia Study Group
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0301 basic medicine ,Adult ,Glycerol ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Ornithine transcarbamylase ,Liver transplantation ,Asymptomatic ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Cognition ,Neonatal Screening ,Intellectual disability ,medicine ,urea cycle disorders ,diagnosis ,therapy ,cognitive function ,Humans ,Prospective Studies ,Glycerol phenylbutyrate ,Prospective cohort study ,Child ,Urea Cycle Disorders, Inborn ,Newborn screening ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Mental Status and Dementia Tests ,Phenylbutyrates ,Liver Transplantation ,030104 developmental biology ,Cross-Sectional Studies ,Neurology ,chemistry ,Child, Preschool ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Neurocognitive ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
OBJECTIVE Individuals with urea cycle disorders (UCDs) often present with intellectual and developmental disabilities. The major aim of this study was to evaluate the impact of diagnostic and therapeutic interventions on cognitive outcomes in UCDs. METHODS This prospective, observational, multicenter study includes data from 503 individuals with UCDs who had comprehensive neurocognitive testing with a cumulative follow-up of 702 patient-years. RESULTS The mean cognitive standard deviation score (cSDS) was lower in symptomatic than in asymptomatic (p < 0.001, t test) individuals with UCDs. Intellectual disability (intellectual quotient < 70, cSDS < -2.0) was associated with the respective subtype of UCD and early disease onset, whereas height of the initial peak plasma ammonium concentration was inversely associated with neurocognitive outcomes in mitochondrial (proximal) rather than cytosolic (distal) UCDs. In ornithine transcarbamylase and argininosuccinate synthetase 1 deficiencies, we did not find evidence that monoscavenger therapy with sodium or glycerol phenylbutyrate was superior to sodium benzoate in providing cognitive protection. Early liver transplantation appears to be beneficial for UCDs. It is noteworthy that individuals with argininosuccinate synthetase 1 and argininosuccinate lyase deficiencies identified by newborn screening had better neurocognitive outcomes than those diagnosed after the manifestation of first symptoms. INTERPRETATION Cognitive function is related to interventional and non-interventional variables. Early detection by newborn screening and early liver transplantation appear to offer greater cognitive protection, but none of the currently used nitrogen scavengers was superior with regard to long-term neurocognitive outcome. Further confirmation could determine these variables as important clinical indicators of neuroprotection for individuals with UCDs. ANN NEUROL 2019.
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- 2018
4. ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype
- Author
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Lerner, Shaul, Eilam, Raya, Adler, Lital, Baruteau, Julien, Kreiser, Topaz, Tsoory, Michael, Brandis, Alexander, Mehlman, Tevie, Ryten, Mina, Botia, Juan A., Ruiz, Sonia Garcia, Garcia, Alejandro Cisterna, Dionisi-Vici, Carlo, Ranucci, Giusy, Spada, Marco, Mazkereth, Ram, McCarter, Robert, Izem, Rima, Balmat, Thomas J., Richesson, Rachel, Baumgartner, Matthias R., Bedoyan, Jirair K., Berry, Gerard, Berry, Susan A., Burgard, Peter, Burrage, Lindsay, Coughlin, Curtis, Diaz, George A., Enns, Gregory, Gallagher, Renata C., Gropman, Andrea, Harding, Cary O., Hoffmann, Georg, Le Mons, Cynthia, McCandless, Shawn E., Merritt, J. Lawrence, Nagamani, Sandesh C. S., Schulze, Andreas, Seminara, Jennifer, Stricker, Tamar, Tuchman, Mendel, Waisbren, Susan, Weisfeld-Adams, James D., Wong, Derek, Yudkoff, Marc, Gazit, Ehud, and Erez, Ayelet
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0303 health sciences ,Tyrosine hydroxylase ,Pars compacta ,Neurodegeneration ,Dopaminergic ,Substantia nigra ,Biology ,medicine.disease ,Argininosuccinate lyase ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,nervous system ,Genetics ,Catecholamine ,medicine ,Tyrosine ,030217 neurology & neurosurgery ,Genetics (clinical) ,030304 developmental biology ,medicine.drug - Abstract
Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders.
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