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The New England Journal of Medicine Nov 2021
Topics: Humans; Hyperoxaluria, Primary; RNA Interference; RNAi Therapeutics
PubMed: 34758265
DOI: 10.1056/NEJMc2107661 -
Nature Reviews. Nephrology Sep 2021
Topics: Humans; Hyperoxaluria, Primary; Kidney Transplantation
PubMed: 34113016
DOI: 10.1038/s41581-021-00449-9 -
Indian Journal of Pathology &... 2021
Topics: Biopsy; Fatal Outcome; Female; Humans; Hyperoxaluria, Primary; Infant, Newborn; Kidney; Renal Insufficiency
PubMed: 34341288
DOI: 10.4103/IJPM.IJPM_319_20 -
Pediatric Nephrology (Berlin, Germany) May 2023The primary hyperoxalurias (PH1-3) are rare inherited disorders of the glyoxylate metabolism characterized by endogenous overproduction of oxalate. As oxalate cannot be...
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. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Hyperoxaluria, Primary; Oxalates; Retinal Diseases; Phenotype
PubMed: 36260161
DOI: 10.1007/s00467-022-05765-1 -
Nephrology, Dialysis, Transplantation :... Apr 2022Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone...
BACKGROUND
Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2.
METHODS
Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62).
RESULTS
PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients.
CONCLUSIONS
Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.
Topics: Female; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Male; Mutation; Nephrolithiasis; Phenotype; Renal Insufficiency
PubMed: 33543760
DOI: 10.1093/ndt/gfab027 -
American Journal of Ophthalmology Oct 2019To investigate ophthalmic features in a large group of patients with primary hyperoxaluria type 1 (PH1) and to determine the relation between ocular involvement and...
PURPOSE
To investigate ophthalmic features in a large group of patients with primary hyperoxaluria type 1 (PH1) and to determine the relation between ocular involvement and systemic disease severity.
DESIGN
Retrospective, cross-sectional, multicenter study of the OxalEurope Registry Network.
METHODS
Sixty-eight patients with PH1 were included. Infantile PH1 was diagnosed in 12 patients, and non-infantile PH1 was diagnosed in 56 patients (17 with end-stage renal disease). Ophthalmic examination included best corrected visual acuity (BCVA) testing and multimodal retinal imaging, including fundus photography and optical coherence tomography (OCT). In selected cases, fundus autofluorescence imaging was performed.
RESULTS
All eyes (n = 24) of infantile PH1 patients revealed severe retinal alterations and oxalate deposits, including macular crystals and hyperpigmentations (n = 9, 38%), and subretinal fibrosis (n = 15, 63%) with (n = 7, 47%) or without (n = 8; 53%) associated chronic retinal edema. In 9 eyes (38%, all with subretinal fibrosis), BCVA was significantly reduced (<20/50 Snellen equivalent). In contrast, all eyes (n = 112) of patients with non-infantile PH1 had a BCVA in the normal range (median, 20/20). Only 6 patients with non-infantile disease (11%, all with end-stage renal disease) showed mild, likely PH1-related retinal features. These deposits appeared as focal hyperreflective subretinal lesions on OCT imaging and were hyperautofluorescent on autofluorescence images.
CONCLUSIONS
Severe ocular alterations occur in infantile cases, whereas mild or no ocular alterations are typical in non-infantile PH1 patients. The natural history of (sub)retinal oxalate deposits, the pathogenesis of subretinal fibrosis, and exact factors influencing the overall severity of ocular disease manifestation remain to be determined.
Topics: Adolescent; Adult; Child; Child, Preschool; Cross-Sectional Studies; Disease Progression; Female; Fluorescein Angiography; Fundus Oculi; Humans; Hyperoxaluria, Primary; Infant; Infant, Newborn; Male; Middle Aged; Oxalates; Phenotype; Retina; Retinal Diseases; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 31078535
DOI: 10.1016/j.ajo.2019.04.036 -
Biomolecules Apr 2024Primary hyperoxalurias (PHs) are inherited metabolic disorders marked by enzymatic cascade disruption, leading to excessive oxalate production that is subsequently... (Review)
Review
Primary hyperoxalurias (PHs) are inherited metabolic disorders marked by enzymatic cascade disruption, leading to excessive oxalate production that is subsequently excreted in the urine. Calcium oxalate deposition in the renal tubules and interstitium triggers renal injury, precipitating systemic oxalate build-up and subsequent secondary organ impairment. Recent explorations of novel therapeutic strategies have challenged and necessitated the reassessment of established management frameworks. The execution of diverse clinical trials across various medication classes has provided new insights and knowledge. With the evolution of PH treatments reaching a new milestone, prompt and accurate diagnosis is increasingly critical. Developing early, effective management and treatment plans is essential to improve the long-term quality of life for PH patients.
Topics: Humans; Hyperoxaluria, Primary; Calcium Oxalate; Oxalates; Quality of Life
PubMed: 38785918
DOI: 10.3390/biom14050511 -
Archives of Disease in Childhood Jun 2000
Review
Topics: Child; Child, Preschool; Fluid Therapy; Genetic Therapy; Humans; Hyperoxaluria, Primary; Kidney Transplantation; Liver Transplantation; Prenatal Diagnosis; Prognosis; Renal Dialysis
PubMed: 10833178
DOI: 10.1136/adc.82.6.470 -
Transplantation Apr 2021
Topics: Adolescent; Humans; Hyperoxaluria, Primary; Liver Transplantation; Male; Postoperative Complications; RNA, Small Interfering; RNAi Therapeutics; Risk Factors; Treatment Outcome
PubMed: 33760795
DOI: 10.1097/TP.0000000000003597 -
Ugeskrift For Laeger Jul 1989Primary hyperoxaluria is a recessive hereditary disturbance of glyoxylate metabolism caused by deficiency of the liver enzyme, alanine glyoxylate transaminase. The main... (Review)
Review
Primary hyperoxaluria is a recessive hereditary disturbance of glyoxylate metabolism caused by deficiency of the liver enzyme, alanine glyoxylate transaminase. The main symptoms are recurrent renal stones, nephrocalcinosis and renal failure. In the advanced state, the disease is frequently complicated by osseous disease, vascular insufficiency and cardiac arrhytmias caused by deposits of calcium oxalate in the tissue. The prognosis is poor. No specific medical treatment exists. Dialysis is not effective and the results of renal transplantation is poor. Combined liver and renal transplantation correct the metabolic defect and the excretion of oxalate is normalised. Combined transplantation must be regarded as the optimal treatment of renal failure caused by PHO. The transplantation should be undertaken preferably before the creatinine clearance falls below 10-20 ml/min in order to avoid tissue deposits of calcium oxalate and excessive urinary excretion of oxalate during immediate post-transplantation period.
Topics: Adult; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Male
PubMed: 2672487
DOI: No ID Found