A review of treatment modalities in gyrate atrophy of the choroid and retina (GACR).

Autor: Balfoort BM; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Buijs MJN; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Ten Asbroek ALMA; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Bergen AAB; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands; Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Boon CJF; Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands; Department of Ophthalmology, Leiden University Medical Centre, 2333, ZA, Leiden, the Netherlands., Ferreira EA; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Wagenmakers MAEM; Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Centre Rotterdam, the Netherlands., Wanders RJA; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Waterham HR; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., Timmer C; Department Endocrinology and Metabolism Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands., van Karnebeek CD; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands; Department of Paediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands., Brands MM; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105, AZ, Amsterdam, the Netherlands. Electronic address: m.m.brands@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2021 Sep-Oct; Vol. 134 (1-2), pp. 96-116. Date of Electronic Publication: 2021 Jul 26.
DOI: 10.1016/j.ymgme.2021.07.010
Abstrakt: Gyrate atrophy of the choroid and retina (GACR) is a rare inborn error of amino acid metabolism caused by bi-allelic variations in OAT. GACR is characterised by vision decline in early life eventually leading to complete blindness, and high plasma ornithine levels. There is no curative treatment for GACR, although several therapeutic modalities aim to slow progression of the disease by targeting different steps within the ornithine pathway. No international treatment protocol is available. We systematically collected all international literature on therapeutic interventions in GACR to provide an overview of published treatment effects.
Methods: Following the PRISMA guidelines, we conducted a systematic review of the English literature until December 22nd 2020. PubMed and Embase databases were searched for studies related to therapeutic interventions in patients with GACR.
Results: A total of 33 studies (n = 107 patients) met the inclusion criteria. Most studies were designed as case reports (n = 27) or case series (n = 4). No randomised controlled trials or large cohort studies were found. Treatments applied were protein-restricted diets, pyridoxine supplementation, creatine or creatine precursor supplementation, l-lysine supplementation, and proline supplementation. Protein-restricted diets lowered ornithine levels ranging from 16.0-91.2%. Pyridoxine responsiveness was reported in 30% of included mutations. Lysine supplementation decreased ornithine levels with 21-34%. Quality assessment showed low to moderate quality of the articles.
Conclusions: Based primarily on case reports ornithine levels can be reduced by using a protein restricted diet, pyridoxine supplementation (variation-dependent) and/or lysine supplementation. The lack of pre-defined clinical outcome measures and structural follow-up in all included studies impeded conclusions on clinical effectiveness. Future research should be aimed at 1) Unravelling the OAT biochemical pathway to identify other possible pathologic metabolites besides ornithine, 2) Pre-defining GACR specific clinical outcome measures, and 3) Establishing an international historical cohort.
Competing Interests: Declaration of Competing Interest The authors report no conflict of interest.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: