INTRODUCTION: Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. PATIENTS AND METHODS: Four patients with MMA (mut° phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40ml/min/1.73m(2)) but normal renal function in one (eGFR of 93ml/min/1.73m(2)) before transplantation. RESULTS: The medium age at transplantation was 7.9y (5-10.2) and the median follow-up was 2.8years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530μmol/L versus 240μmol/L after transplantation, and mean values of urine MMA before transplantation 4700mmol/mol creatinine versus 2300mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83g/Kg/day. One patient transplanted at age 9.7years developed a hepatoblastoma at age 11years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. CONCLUSION: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible.
INTRODUCTION:Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. PATIENTS AND METHODS: Four patients with MMA (mut° phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40ml/min/1.73m(2)) but normal renal function in one (eGFR of 93ml/min/1.73m(2)) before transplantation. RESULTS: The medium age at transplantation was 7.9y (5-10.2) and the median follow-up was 2.8years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530μmol/L versus 240μmol/L after transplantation, and mean values of urine MMA before transplantation 4700mmol/mol creatinine versus 2300mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83g/Kg/day. One patient transplanted at age 9.7years developed a hepatoblastoma at age 11years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. CONCLUSION: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible.
Authors: Hilary J Vernon; C John Sperati; Joshua D King; Andrea Poretti; Neil R Miller; Jennifer L Sloan; Andrew M Cameron; Donna Myers; Charles P Venditti; David Valle Journal: J Inherit Metab Dis Date: 2014-06-25 Impact factor: 4.982
Authors: Irini Manoli; Justin R Sysol; Lingli Li; Pascal Houillier; Caterina Garone; Cindy Wang; Patricia M Zerfas; Kristina Cusmano-Ozog; Sarah Young; Niraj S Trivedi; Jun Cheng; Jennifer L Sloan; Randy J Chandler; Mones Abu-Asab; Maria Tsokos; Abdel G Elkahloun; Seymour Rosen; Gregory M Enns; Gerard T Berry; Victoria Hoffmann; Salvatore DiMauro; Jurgen Schnermann; Charles P Venditti Journal: Proc Natl Acad Sci U S A Date: 2013-07-29 Impact factor: 11.205
Authors: Marianna Caterino; Randy J Chandler; Jennifer L Sloan; Kenneth Dorko; Kristina Cusmano-Ozog; Laura Ingenito; Stephen C Strom; Esther Imperlini; Emanuela Scolamiero; Charles P Venditti; Margherita Ruoppolo Journal: Mol Biosyst Date: 2016-02
Authors: Matthias R Baumgartner; Friederike Hörster; Carlo Dionisi-Vici; Goknur Haliloglu; Daniela Karall; Kimberly A Chapman; Martina Huemer; Michel Hochuli; Murielle Assoun; Diana Ballhausen; Alberto Burlina; Brian Fowler; Sarah C Grünert; Stephanie Grünewald; Tomas Honzik; Begoña Merinero; Celia Pérez-Cerdá; Sabine Scholl-Bürgi; Flemming Skovby; Frits Wijburg; Anita MacDonald; Diego Martinelli; Jörn Oliver Sass; Vassili Valayannopoulos; Anupam Chakrapani Journal: Orphanet J Rare Dis Date: 2014-09-02 Impact factor: 4.123