Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy

Orphanet Journal of Rare Diseases

Research

Alison Woodall¹  Gisela Wilcox¹  Karolina M. Stepien¹  Christopher Campbell²  Stephanie Barton²  Eleanor Palmer³  Christos Iosifidis³  Panagiotis I. Sergouniotis⁴  Graeme C. Black⁴  Arunabha Ghosh⁵  Alexander Broomfield⁵ 

[1] Adult Inherited Metabolic Disorders, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, UK;Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;Manchester Centre for Genomic Medicine, Saint Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK;Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK;Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK;Manchester Centre for Genomic Medicine, Saint Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK;Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;Willink Biochemical Genetics, Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK;

关键词: Gyrate atrophy;    Inborn errors of metabolism;    Inherited retinal disorders;    Hyperornithinaemia;    Ornithine aminotransferase deficiency;    OAT;   

DOI  :  10.1186/s13023-023-02840-0

 received in 2023-01-31, accepted in 2023-07-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene, encoding the enzyme ornithine δ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithinaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy.MethodsStudy participants were recruited through a tertiary UK clinical ophthalmic genetic service. All cases had a biochemical and molecular diagnosis of gyrate atrophy. Retrospective phenotypic and biochemical data were collected using electronic healthcare records.Results18 affected individuals from 12 families (8 male, 10 female) met the study inclusion criteria. The median age at diagnosis was 8 years (range 10 months – 33 years) and all cases had hyperornithinaemia (median: 800 micromoles/L; range: 458–1244 micromoles/L). Common features at presentation included high myopia (10/18) and nyctalopia (5/18). Ophthalmic findings were present in all study participants who were above the age of 6 years. One third of patients had co-existing macular oedema and two thirds developed pre-senile cataracts. Compliance with dietary modifications was suboptimal in most cases. A subset of participants had extraocular features including a trend towards reduced fat-free mass and developmental delay.ConclusionsOur findings highlight the importance of multidisciplinary care in families with gyrate atrophy. Secondary ophthalmic complications such as macular oedema and cataract formation are common. Management of affected individuals remains challenging due to the highly restrictive nature of the recommended diet and the limited evidence-base for current strategies.

【 授权许可】

CC BY   
© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

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