Progressive development of renal cysts in glycogen storage disease type I
| Autor: | Mylène Mabille, Philippe Labrune, Marie Brevet, Coralie Pelissou, Gilles Mithieux, Laurence Dubourg, Louis Lassalle, Ariane Perry, Monika Gjorgjieva, A. Stefanutti, Antonin Tortereau, Margaux Raffin, A. Duchampt, Fabienne Rajas, Aurélie Hubert-Buron |
|---|---|
| Přispěvatelé: | Di Carlo, Marie-Ange, Nutrition, diabète et cerveau (NUDICE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence Maladies Héréditaires du Métabolisme Hépatique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie [Hospices civils de Lyon], Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Nutrition, diabète et cerveau |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Pathology Adolescent 030232 urology & nephrology Glycogen Storage Disease Type I Biology urologic and male genital diseases Nephropathy Gene Knockout Techniques Mice Young Adult 03 medical and health sciences 0302 clinical medicine Glomerular Filtration Barrier Fibrosis Internal medicine Genetics medicine Polycystic kidney disease Animals Humans Cyst Renal Insufficiency [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Child Molecular Biology Genetics (clinical) Glycogen storage disease type I Kidney Infant General Medicine Kidney Diseases Cystic Middle Aged medicine.disease 3. Good health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Renal pathology Child Preschool Disease Progression Glucose-6-Phosphatase Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Kidney disease |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, 2016, 25 (17), pp.3784-3797. ⟨10.1093/hmg/ddw224⟩ Human Molecular Genetics, Oxford University Press (OUP), 2016, 25 (17), pp.3784-3797. ⟨10.1093/hmg/ddw224⟩ |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddw224 |
| Popis: | International audience; Glycogen storage disease type I (GSDI) is a rare metabolic disease due to glucose-6 phosphatase deficiency, characterized by fasting hypoglycemia. Patients also develop chronic kidney disease whose mechanisms are poorly understood. To decipher the process, we generated mice with a kidney-specific knockout of glucose-6 phosphatase (K.G6pc-/- mice) that exhibited the first signs of GSDI nephropathy after 6 months of G6pc deletion. We studied the natural course of renal deterioration in K.G6pc-/- mice for 18 months and observed the progressive deterioration of renal functions characterized by early tubular dysfunction and a later destruction of the glomerular filtration barrier. After 15 months, K.G6pc-/- mice developed tubular-glomerular fibrosis and podocyte injury, leading to the development of cysts and renal failure. On the basis of these findings, we were able to detect the development of cysts in 7 out of 32 GSDI patients, who developed advanced renal impairment. Of these 7 patients, 3 developed renal failure. In addition, no renal cysts were detected in six patients who showed early renal impairment. In conclusion, renal pathology in GSDI is characterized by progressive tubular dysfunction and the development of polycystic kidneys that probably leads to the development of irreversible renal failure in the late stages. Systematic observations of cyst development by kidney imaging should improve the evaluation of the disease's progression, independently of biochemical markers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|