title: Progressive development of renal cysts in glycogen storage disease type I.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Gjorgjieva
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Raffin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Duchampt
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique, Clamart, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Perry
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Stefanutti
authors.affiliation: Université de Lyon, Lyon, France.|Service de pathologie et de neuropathologie Est, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Brevet
authors.affiliation: Université de Lyon, Lyon, France.|VetAgro Sup, UPSP 2011-03-101, ICE, Marcy L'Etoile, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Tortereau
authors.affiliation: Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.|UMR 5305 CNRS/Université Claude-Bernard, Biologie tissulaire et Ingénierie thérapeutique, Lyon, France.|Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices civils de Lyon, Lyon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dubourg
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique, Clamart, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hubert-Buron
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de radiologie, Clamart, France.|Université Paris Sud, Orsay, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Mabille
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de radiologie, Clamart, France.|Université Paris Sud, Orsay, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Pelissou
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de radiologie, Clamart, France.|Université Paris Sud, Orsay, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Lassalle
authors.affiliation: APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique, Clamart, France.|Université Paris Sud, Orsay, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Labrune
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France fabienne.rajas@univ-lyon1.fr.|Université de Lyon, Lyon, France.|Université Lyon1, Villeurbanne, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Rajas
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055786:Gene Knockout Techniques; D060730:Glomerular Filtration Barrier / Q000473:pathology* / Q000503:physiopathology; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D005953:Glycogen Storage Disease Type I / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D051437:Renal Insufficiency / Q000209:etiology* / Q000473:pathology; D055815:Young Adult
chemical_list: D005952:Glucose-6-Phosphatase