title: Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte (MaMEA), Hôpital Necker-Enfants Malades, Université Paris Descartes, Institut Imagine, France.
authors.forename: A
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authors.lastname: Brassier
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authors.lastname: Valayannopoulos
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authors.lastname: Ottolenghi
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authors.forename: M A
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authors.lastname: Desguerre
authors.forename: M
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authors.lastname: Charbit
authors.forename: J F
authors.initials: JF
authors.lastname: Benoist
authors.forename: L
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authors.lastname: Aigrain
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authors.lastname: Blanc
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authors.lastname: Salomon
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authors.lastname: Rabier
authors.forename: G
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mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000652:urine; D064987:Cell- and Tissue-Based Therapy; D002648:Child; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics / Q000628:therapy*; D008764:Methylmalonic Acid / Q000097:blood / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology / Q000628:therapy*
chemical_list: D008764:Methylmalonic Acid
keywords: CKD; Chronic renal disease; DQ; IQ; MMA; MRI; Methylmalonic acidemia; Renal transplantation; chronic kidney disease; development quotient; eGFR; glomerular filtration rate; intellectual quotient; magnetic resonance imaging; methylmalonic aciduria