[en] INTRODUCTION: Primary hyperoxaluria type 1 (PH1) is known for its variable clinical course, even within families. However, the extent of this heterogeneity has not been well-studied. We aimed to analyze intrafamilial clinical heterogeneity and disease course among siblings in a large cohort of familial PH1 cases. METHODS: A retrospective registry study was performed using data from OxalEurope. All PH1 families with 2 or more affected siblings were included. A 6-point PH1 clinical outcome scoring system was developed to grade heterogeneity within a family. Intrafamilial clinical heterogeneity was defined as a score ≥2. Kaplan-Meier analyses were used to analyze differences in kidney survival between index cases and siblings. RESULTS: We included 88 families, encompassing 193 patients with PH1. The median interquartile range (IQR) follow-up time was 7.8 (1.9-17) years. Intrafamilial clinical heterogeneity, as defined by our score, was found in 38 (43%) PH1 families. In 54% of the families, affected siblings had a better outcome than the index case. Clinically asymptomatic siblings at the time of their diagnosis had a significantly more favorable clinical outcome based on the authors' scoring system than siblings with clinical signs and index cases (P < 0.001). Kaplan-Meier analyses revealed that index cases reached kidney failure at an earlier age and earlier in follow-up compared to siblings (P < 0.001). CONCLUSIONS: Intrafamilial clinical heterogeneity was found in a substantial number of familial PH1 cases. Compared to index cases, siblings had significantly better clinical outcomes and kidney survival; thereby supporting the policy of family screening to diagnose affected siblings early to improve their prognosis.
Disciplines :
Urology & nephrology Pediatrics
Author, co-author :
Deesker, Lisa J; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Karacoban, Hazal A; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Metry, Elisabeth L; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Garrelfs, Sander F; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Bacchetta, Justine; Centre de Référence des Maladies Rénales Rares, Hospices Civils de Lyon and Université Claude-Bernard Lyon 1, INSERM 1033 Unit, Lyon, France.
Boyer, Olivia; Néphrologie Pédiatrique, Centre de Référence MARHEA, Institut Imagine, Université Paris Cité, Hôpital Necker-Enfants Malades, Paris, France.
Collard, Laure ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Devresse, Arnaud; Department of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Hayes, Wesley; Department of Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Hulton, Sally-Anne; Department of Nephrology, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, UK.
Martin-Higueras, Cristina; Institute of Biomedical Technology, CIBERER, University of Laguna, San Cristóbal de La Laguna, Spain.
Moochhala, Shabbir H; UCL Department of Renal Medicine, Royal Free Hospital, London, UK.
Neuhaus, Thomas J; Department of Pediatrics, Children's Hospital Lucerne, Lucerne, Switzerland.
Oh, Jun; Department of Pediatric Nephrology, Medical University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Prikhodina, Larisa; Department of Inherited and Acquired Kidney Diseases, Veltishev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University, Moscow, Russia.
Sikora, Przemyslaw; Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland.
Oosterveld, Michiel J S; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Groothoff, Jaap W; Department of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
Mandrile, Giorgia; Genetic Unit and Thalassemia Center, San Luigi University Hospital, Orbassano, Italy.
Beck, Bodo B; Institute of Human Genetics, Center for Molecular Medicine Cologne, University Hospital of Cologne, Cologne, Germany. ; Center for Rare and Hereditary Kidney Disease Cologne, University Hospital of Cologne, Cologne, Germany.
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