Clinical phenotype, biochemical profile, and treatment in 19 patients with arginase 1 deficiency
| Autor: | Nina L. Schrager, Brunhilde Riesner, Markus G. Donner, Hanno Ulmer, Jaime M. Brum, Turgay Coşkun, Özlem Ünal, Andrea Schlune, Johannes Häberle, James D. Weisfeld-Adams, Sabine Scholl-Bürgi, Martina Huemer, Daniel R. Carvalho, Claudio Gemperle, Daniela Karall, Martin Hersberger |
|---|---|
| Přispěvatelé: | University of Zurich, Huemer, Martina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Pathology 2716 Genetics (clinical) Adolescent Nitric Oxide Synthase Type III Urea cycle disorder Glycine Nitric Oxide Synthase Type II Hyperargininemia 610 Medicine & health Biology Arginine Nitric Oxide complex mixtures Young Adult 03 medical and health sciences 0302 clinical medicine 1311 Genetics Molecular genetics Genetics medicine Humans Amino Acids Child ARG1 Urea Cycle Disorders Inborn Genetics (clinical) Retrospective Studies Arginase Case-control study Infant Retrospective cohort study Middle Aged medicine.disease Human genetics 3. Good health Oxidative Stress Phenotype 030104 developmental biology 10036 Medical Clinic Case-Control Studies Child Preschool Immunology Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of inherited metabolic disease |
| DOI: | 10.1007/s10545-016-9928-y |
| Popis: | Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD). This hypothesis-generating study explored clinical phenotypes, metabolic profiles, molecular genetics, and treatment approaches in a cohort of children and adults with ARG1 deficiency to add to our understanding of the underlying pathophysiology.Clinical data were retrieved retrospectively from physicians using a questionnaire survey. Plasma aminoacids, guanidinoacetate (GAA), parameters indicating oxidative stress and nitric oxide (NO) synthesis as well as asymmetric dimethylarginine (ADMA) were measured at a single study site.Nineteen individuals with ARG1 deficiency and 19 matched controls were included in the study. In patients, paraparesis, cognitive impairment, and seizures were significantly associated suggesting a shared underlying pathophysiology. In patients plasma GAA exceeded normal ranges and plasma ADMA was significantly elevated. Compared to controls, nitrate was significantly higher, and the nitrite:nitrate ratio significantly lower in subjects with ARG1 deficiency suggesting an advantage for NO synthesis by inducible NO synthase (iNOS) over endothelial NOS (eNOS). Logistic regression revealed no significant impact of any of the biochemical parameters (including arginine, nitrates, ADMA, GAA, oxidative stress) or protein restriction on long-term outcome.Three main hypotheses which must be evaluated in a hypothesis driven confirmatory study are delineated from this study: 1) clinical manifestations in ARG1 deficiency are not correlated with arginine, protein intake, ADMA, nitrates or oxidative stress. 2) GAA is elevated and may be a marker or an active part of the pathophysiology of ARG1 deficiency. 3) Perturbations of NO metabolism merit future attention in ARG1 deficiency. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|