TY - JOUR
T1 - A review of treatment modalities in gyrate atrophy of the choroid and retina (GACR)
AU - Balfoort, Berith M.
AU - Buijs, Mark J.N.
AU - ten Asbroek, Anneloor L.M.A.
AU - Bergen, Arthur A.B.
AU - Boon, Camiel J.F.
AU - Ferreira, Elise A.
AU - Houtkooper, Riekelt H.
AU - Wagenmakers, Margreet A.E.M.
AU - Wanders, Ronald J.A.
AU - Waterham, Hans R.
AU - Timmer, Corrie
AU - van Karnebeek, Clara D.
AU - Brands, Marion M.
N1 - Funding Information:
PhD salaries of M.J.N. Buijs and B.M. Balfoort were funded by: Amsterdam Gastroenterology & Metabolism Institute (Amsterdam UMC), Stichting Steun Emma Kinderziekenhuis, Horstingstuit Foundation via AMC Foundation, Stichting Metakids.
Publisher Copyright:
© 2021 The Authors
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111567757&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2021.07.010
DO - 10.1016/j.ymgme.2021.07.010
M3 - Review article
C2 - 34340878
AN - SCOPUS:85111567757
SN - 1096-7192
VL - 134
SP - 96
EP - 116
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -
