OBJECTIVE: To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN: Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4-19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies. RESULTS: Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5-18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2-7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut(o), 3 mut- and 5 cblA. Mortality, number of acute decompensations (p=0.031), median MMA urinary excretion (p=0.006) and neurological impairment (p<0.0001) were higher in mut degrees patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut(o) patients and was more severe. CONCLUSIONS: Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut(o) phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
OBJECTIVE: To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN: Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4-19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies. RESULTS: Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5-18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2-7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut(o), 3 mut- and 5 cblA. Mortality, number of acute decompensations (p=0.031), median MMA urinary excretion (p=0.006) and neurological impairment (p<0.0001) were higher in mut degrees patients compared to mut-/cblApatients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut(o) patients and was more severe. CONCLUSIONS: Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut(o) phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
Authors: Stefan Kölker; Vassili Valayannopoulos; Alberto B Burlina; Jolanta Sykut-Cegielska; Frits A Wijburg; Elisa Leão Teles; Jiri Zeman; Carlo Dionisi-Vici; Ivo Barić; Daniela Karall; Jean-Baptiste Arnoux; Paula Avram; Matthias R Baumgartner; Javier Blasco-Alonso; S P Nikolas Boy; Marlene Bøgehus Rasmussen; Peter Burgard; Brigitte Chabrol; Anupam Chakrapani; Kimberly Chapman; Elisenda Cortès I Saladelafont; Maria L Couce; Linda de Meirleir; Dries Dobbelaere; Francesca Furlan; Florian Gleich; Maria Julieta González; Wanda Gradowska; Stephanie Grünewald; Tomas Honzik; Friederike Hörster; Hariklea Ioannou; Anil Jalan; Johannes Häberle; Gisela Haege; Eveline Langereis; Pascale de Lonlay; Diego Martinelli; Shirou Matsumoto; Chris Mühlhausen; Elaine Murphy; Hélène Ogier de Baulny; Carlos Ortez; Consuelo C Pedrón; Guillem Pintos-Morell; Luis Pena-Quintana; Danijela Petković Ramadža; Esmeralda Rodrigues; Sabine Scholl-Bürgi; Etienne Sokal; Marshall L Summar; Nicholas Thompson; Roshni Vara; Inmaculada Vives Pinera; John H Walter; Monique Williams; Allan M Lund; Angeles Garcia-Cazorla; Angeles Garcia Cazorla Journal: J Inherit Metab Dis Date: 2015-04-15 Impact factor: 4.982
Authors: Zsuzsanna K Zsengellér; Nika Aljinovic; Lisa A Teot; Mark Korson; Nancy Rodig; Jennifer L Sloan; Charles P Venditti; Gerard T Berry; Seymour Rosen Journal: Pediatr Nephrol Date: 2014-05-28 Impact factor: 3.714
Authors: Jens C Koenig; Frank Rutsch; Clemens Bockmeyer; Matthias Baumgartner; Bodo B Beck; Brigitta Kranz; Martin Konrad Journal: Pediatr Nephrol Date: 2015-04-18 Impact factor: 3.714
Authors: Elizabeth A Harrington; Jennifer L Sloan; Irini Manoli; Randy J Chandler; Mark Schneider; Peter J McGuire; Roberto Calcedo; James M Wilson; Charles P Venditti Journal: Hum Gene Ther Date: 2016-03-22 Impact factor: 5.695
Authors: Erin A Paul; Marta Guttenberg; Paige Kaplan; David Watkins; David S Rosenblatt; James R Treat; Bernard S Kaplan Journal: Pediatr Nephrol Date: 2013-03-19 Impact factor: 3.714