Journal article
Clinical phenotype, biochemical profile, and treatment in 19 patients with arginase 1 deficiency.
- Huemer M Division of Metabolic Diseases and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. martina.huemer@lkhb.at.
- Carvalho DR Genetic Unit, SARAH Network of Rehabilitation Hospital, Brasilia, Brazil.
- Brum JM Molecular Pathology Department, Rede Sarah de Hospitais de Reabilitação, Brasilia, Brazil.
- Ünal Ö Department of Paediatrics, Division of Paediatric Nutrition and Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey.
- Coskun T Department of Paediatrics, Division of Paediatric Nutrition and Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey.
- Weisfeld-Adams JD Program for Inherited Metabolic Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Schrager NL Program for Inherited Metabolic Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Scholl-Bürgi S Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.
- Schlune A Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University, Düsseldorf, Germany.
- Donner MG Department of Gastroenterology, Hepatology and Infectious diseases, Heinrich Heine University, Düsseldorf, Germany.
- Hersberger M Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
- Gemperle C Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
- Riesner B Department of Paediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria.
- Ulmer H Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
- Häberle J Division of Metabolic Diseases and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
- Karall D Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.
- 2016-04-03
Published in:
- Journal of inherited metabolic disease. - 2016
Adolescent
Adult
Amino Acids
Arginase
Arginine
Case-Control Studies
Child
Child, Preschool
Female
Glycine
Humans
Infant
Male
Middle Aged
Nitric Oxide
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Oxidative Stress
Phenotype
Retrospective Studies
Urea Cycle Disorders, Inborn
Young Adult
English
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1007/s10545-016-9928-y
- PMID 27038030
- Persistent URL
- https://sonar.ch/global/documents/228929
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