TY - JOUR
T1 - The retinal phenotype in primary hyperoxaluria type 2 and 3
AU - Birtel, Johannes
AU - Diederen, Roselie M.
AU - Herrmann, Philipp
AU - Kaspar, Sophie
AU - Beck, Bodo B.
AU - Garrelfs, Sander F.
AU - Hoppe, Bernd
AU - Charbel Issa, Peter
N1 - Funding Information: JB has been a consultant of Alnylam Pharmaceuticals, Cambridge, MA, USA, and has received a grant from Dicerna Pharmaceuticals, a Novo Nordisk subsidiary, Lexington, MA, USA. PH has received honoraria for lectures from Novartis und Bayer and has received a grant from Novartis. BH has been an employee of Dicerna Pharmaceuticals, a Novo Nordisk subsidiary, Lexington, MA, USA. BBB has received consultation fees from Alnylam Pharmaceuticals, Cambridge, MA, USA. SFG has received grants from Alnylam Pharmaceuticals, Cambridge, MA, USA, and Dicerna Pharmaceuticals, a Novo Nordisk subsidiary, Lexington, MA, USA. The other authors declare no conflicts of interest. Funding Information: This work was supported by Dicerna Pharmaceuticals, the Dr. Werner Jackstädt Foundation, Wuppertal, Germany, (Grant S0134-10.22 to JB), the Bayer Global Ophthalmology Awards Program (JB), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: © 2022, The Author(s).
PY - 2023/5
Y1 - 2023/5
N2 - Background: The primary hyperoxalurias (PH1-3) are rare inherited disorders of the glyoxylate metabolism characterized by endogenous overproduction of oxalate. As oxalate cannot be metabolized by humans, oxalate deposits may affect various organs, primarily the kidneys, bones, heart, and eyes. Vision loss induced by severe retinal deposits is commonly seen in infantile PH1; less frequently and milder retinal alterations are found in non-infantile PH1. Retinal disease has not systematically been investigated in patients with PH2 and PH3. Methods: A comprehensive ophthalmic examination was performed in 19 genetically confirmed PH2 (n = 7) and PH3 (n = 12) patients (median age 11 years, range 3–59). Results: Median best corrected visual acuity was 20/20. In 18 patients, no retinal oxalate deposits were found. A 30-year-old male with PH2 on maintenance hemodialysis with plasma oxalate (Pox) elevation (> 100 µmol/l; normal < 7.4) demonstrated bilateral drusen-like, hyperreflective deposits which were interpreted as crystallized oxalate. Two siblings of consanguineous parents with PH2 presented with retinal degeneration and vision loss; exome-wide analysis identified a second monogenic disease, NR2E3-associated retinal dystrophy. Conclusions: Retinal disease manifestation in PH2 and PH3 is rare but mild changes can occur at least in PH2-associated kidney failure. Decline in kidney function associated with elevated plasma oxalate levels could increase the risk of systemic oxalosis. Deep phenotyping combined with genomic profiling is vital to differentiate extrarenal disease in multisystem disorders such as PH from independent inherited (retinal) disease. Graphical abstract: [Figure not available: see fulltext.]
AB - Background: The primary hyperoxalurias (PH1-3) are rare inherited disorders of the glyoxylate metabolism characterized by endogenous overproduction of oxalate. As oxalate cannot be metabolized by humans, oxalate deposits may affect various organs, primarily the kidneys, bones, heart, and eyes. Vision loss induced by severe retinal deposits is commonly seen in infantile PH1; less frequently and milder retinal alterations are found in non-infantile PH1. Retinal disease has not systematically been investigated in patients with PH2 and PH3. Methods: A comprehensive ophthalmic examination was performed in 19 genetically confirmed PH2 (n = 7) and PH3 (n = 12) patients (median age 11 years, range 3–59). Results: Median best corrected visual acuity was 20/20. In 18 patients, no retinal oxalate deposits were found. A 30-year-old male with PH2 on maintenance hemodialysis with plasma oxalate (Pox) elevation (> 100 µmol/l; normal < 7.4) demonstrated bilateral drusen-like, hyperreflective deposits which were interpreted as crystallized oxalate. Two siblings of consanguineous parents with PH2 presented with retinal degeneration and vision loss; exome-wide analysis identified a second monogenic disease, NR2E3-associated retinal dystrophy. Conclusions: Retinal disease manifestation in PH2 and PH3 is rare but mild changes can occur at least in PH2-associated kidney failure. Decline in kidney function associated with elevated plasma oxalate levels could increase the risk of systemic oxalosis. Deep phenotyping combined with genomic profiling is vital to differentiate extrarenal disease in multisystem disorders such as PH from independent inherited (retinal) disease. Graphical abstract: [Figure not available: see fulltext.]
KW - Kidney failure
KW - Optical coherence tomography
KW - Phenotyping
KW - Plasma oxalate
KW - Primary hyperoxaluria
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=85140125285&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00467-022-05765-1
DO - https://doi.org/10.1007/s00467-022-05765-1
M3 - Article
C2 - 36260161
SN - 0931-041X
VL - 38
SP - 1485
EP - 1490
JO - Pediatric nephrology (Berlin, Germany)
JF - Pediatric nephrology (Berlin, Germany)
IS - 5
ER -