Peter Zhan Tao Wang1, Chitra Prasad2,3, Carmen Inés Rodriguez Cuellar2, Guido Filler4,5,6,7,8. 1. Department of Surgery, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5W9, Canada. 2. Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, Children's Hospital, London Health Science Centre, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. 3. Children's Health Research Institute, University of Western Ontario, London, ON, N6C 2V5, Canada. 4. Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, Children's Hospital, London Health Science Centre, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. guido.filler@lhsc.on.ca. 5. Children's Health Research Institute, University of Western Ontario, London, ON, N6C 2V5, Canada. guido.filler@lhsc.on.ca. 6. Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N5A 5A5, Canada. guido.filler@lhsc.on.ca. 7. Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5W9, Canada. guido.filler@lhsc.on.ca. 8. Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, ON, Canada. guido.filler@lhsc.on.ca.
Abstract
BACKGROUND: Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations. OBJECTIVE: We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl. CASE DIAGNOSIS: The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L). CONCLUSIONS: It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach.
BACKGROUND: Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations. OBJECTIVE: We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl. CASE DIAGNOSIS: The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L). CONCLUSIONS: It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach.
Authors: Daniela A Braun; Jia Rao; Geraldine Mollet; David Schapiro; Marie-Claire Daugeron; Weizhen Tan; Olivier Gribouval; Olivia Boyer; Patrick Revy; Tilman Jobst-Schwan; Johanna Magdalena Schmidt; Jennifer A Lawson; Denny Schanze; Shazia Ashraf; Jeremy F P Ullmann; Charlotte A Hoogstraten; Nathalie Boddaert; Bruno Collinet; Gaëlle Martin; Dominique Liger; Svjetlana Lovric; Monica Furlano; I Chiara Guerrera; Oraly Sanchez-Ferras; Jennifer F Hu; Anne-Claire Boschat; Sylvia Sanquer; Björn Menten; Sarah Vergult; Nina De Rocker; Merlin Airik; Tobias Hermle; Shirlee Shril; Eugen Widmeier; Heon Yung Gee; Won-Il Choi; Carolin E Sadowski; Werner L Pabst; Jillian K Warejko; Ankana Daga; Tamara Basta; Verena Matejas; Karin Scharmann; Sandra D Kienast; Babak Behnam; Brendan Beeson; Amber Begtrup; Malcolm Bruce; Gaik-Siew Ch'ng; Shuan-Pei Lin; Jui-Hsing Chang; Chao-Huei Chen; Megan T Cho; Patrick M Gaffney; Patrick E Gipson; Chyong-Hsin Hsu; Jameela A Kari; Yu-Yuan Ke; Cathy Kiraly-Borri; Wai-Ming Lai; Emmanuelle Lemyre; Rebecca Okashah Littlejohn; Amira Masri; Mastaneh Moghtaderi; Kazuyuki Nakamura; Fatih Ozaltin; Marleen Praet; Chitra Prasad; Agnieszka Prytula; Elizabeth R Roeder; Patrick Rump; Rhonda E Schnur; Takashi Shiihara; Manish D Sinha; Neveen A Soliman; Kenza Soulami; David A Sweetser; Wen-Hui Tsai; Jeng-Daw Tsai; Rezan Topaloglu; Udo Vester; David H Viskochil; Nithiwat Vatanavicharn; Jessica L Waxler; Klaas J Wierenga; Matthias T F Wolf; Sik-Nin Wong; Sebastian A Leidel; Gessica Truglio; Peter C Dedon; Annapurna Poduri; Shrikant Mane; Richard P Lifton; Maxime Bouchard; Peter Kannu; David Chitayat; Daniella Magen; Bert Callewaert; Herman van Tilbeurgh; Martin Zenker; Corinne Antignac; Friedhelm Hildebrandt Journal: Nat Genet Date: 2017-08-14 Impact factor: 38.330
Authors: Simon Edvardson; Laurence Prunetti; Aiman Arraf; Drago Haas; Jo Marie Bacusmo; Jennifer F Hu; Asas Ta-Shma; Peter C Dedon; Valérie de Crécy-Lagard; Orly Elpeleg Journal: Eur J Hum Genet Date: 2017-03-08 Impact factor: 4.246
Authors: Elena Martín-Hernández; M Teresa García-Silva; Julia Vara; Yolanda Campos; Ana Cabello; Rafael Muley; Pilar Del Hoyo; Miguel Angel Martín; Joaquín Arenas Journal: Pediatr Nephrol Date: 2005-06-24 Impact factor: 3.714
Authors: Patrick C Thiaville; Basma El Yacoubi; Ludovic Perrochia; Arnaud Hecker; Magali Prigent; Jennifer J Thiaville; Patrick Forterre; Olivier Namy; Tamara Basta; Valérie de Crécy-Lagard Journal: Eukaryot Cell Date: 2014-07-18
Authors: Konrad M Szymanski; Rosalia Misseri; Benjamin Whittam; James E Lingeman; Sable Amstutz; Joshua D Ring; Martin Kaefer; Richard C Rink; Mark P Cain Journal: J Pediatr Urol Date: 2015-09-25 Impact factor: 1.830
Authors: Andrea Domingo-Gallego; Mónica Furlano; Marc Pybus; Daniel Barraca; Ana Belén Martínez; Emiliano Mora Muñoz; Roser Torra; Elisabet Ars Journal: BMC Nephrol Date: 2019-04-11 Impact factor: 2.388
Authors: Valérie de Crécy-Lagard; Pietro Boccaletto; Carl G Mangleburg; Puneet Sharma; Todd M Lowe; Sebastian A Leidel; Janusz M Bujnicki Journal: Nucleic Acids Res Date: 2019-03-18 Impact factor: 16.971