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Renal transplant in methylmalonic acidemia: could it be the best option?

Report on a case at 10 years and review of the literature

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Abstract

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism. Patients with severe disease develop many complications despite treatment; often, the disease progresses to severe damage of the central nervous system or to end-stage renal disease (ESRD). When medical treatment is ineffective, liver, kidney, or combined liver and kidney transplantation is advocated. At present, there are no definite guidelines as for the organ to be transplanted, and results are inconsistent. We report on a 27-year-old woman with MMA MUT0. The clinical symptoms developed at age 4 months. She progressed to ESRD and received a kidney transplant in November 1996 at age 17 years. One hundred and twenty months after transplant, renal function is normal; although urinary levels of methylmalonic acid are above normal limits, no episodes of metabolic decompensation have been observed after transplantation. Although liver is the major site of methylmalonyl-CoA mutase activity, this case and similar ones in the literature suggest that the smaller mutase activity present in the transplanted kidney may be sufficient to ensure partial correction of the metabolism of organic acids sufficient to prevent the onset of episodes of metabolic decompensation. It is worth investigating whether kidney transplant can be a safer and more satisfactory alternative to liver transplantation in cases of MMA unresponsive to medical treatment although urine MMA excretion remains significantly elevated.

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References

  1. Scriver CR, Beaudet AL, Sly WS, Valle D (2001) The metabolic and molecular basics of inherited disease, 8th edn. McGraw-Hill, New York, pp 1423–1449

    Google Scholar 

  2. de Baulny H, Benoist JF, Rigal O, Touati G, Rabier D, Saudubray JM (2005) Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis 28:415–423

    PubMed  Google Scholar 

  3. Prietsch V, Lindner M, Zschocke J, Nyhan WL, Hoffmann GF (2002) Emergency management of inherited metabolic diseases. J Inherit Metab Dis 25:531–546

    CAS  PubMed  Google Scholar 

  4. Schaefer F, Straube E, Oh J, Mehls O, Mayatepek E (1999) Dilalysis in neonate with inborn errors of metabolism. Nephrol Dial Transplant 14:910–918

    CAS  PubMed  Google Scholar 

  5. Paik KH, Lee JE, Jin DK (2004) Successful dialysis in a boy with methylmalonic acidemia. Pediatr Nephrol 19:1180–1181

    PubMed  Google Scholar 

  6. Meer SB, van der Poggi F, Spada M, Bonnenfort JP, Ogier H, Hubert P, Depondt E, Rappaport D, Rabier D, Charpentier C (1994) Clinical outcome of long term management of patients with vitamin B12-unresponsive methylmalonic acidemia. J Pediatr 125:903–908

    PubMed  Google Scholar 

  7. Nicolaides P, Leonard JV, Surtees R (1998) The neurological outcome of methylmalonic acidemia. Arch Dis Child 78:508–512

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Baumgartner ER, Viardot C (1995) Long term follow-up of 77 patients with isolated methylmalonic aciduria. J Inherit Metab Dis 18:138–142

    Google Scholar 

  9. Tanpaiboon P (2005) Methylmalonic acidemia (MMA). Mol Genet Metab 85:2–6

    CAS  PubMed  Google Scholar 

  10. De Souza C, Peisowicz AT, Brett EM, Leonard JV (1989) Focal changes in the globi pallidi associated with neurological dysfunction in methylmalonic acideamia. Neuropediatrics 20:199–201

    Google Scholar 

  11. Leonard JV (1995) The management and outcome of propionic and methylmalonic acidemias. J Inherit Metab Dis 18:430–434

    CAS  PubMed  Google Scholar 

  12. Rutledge SL, Geraghty M, Mroczek E, Rosenblatt D, Kohout E (1993) Tubolointerstitial nephritis in methylmalonic acidemia. Pediatr Nephrol 7:81–82

    CAS  PubMed  Google Scholar 

  13. D’Angio CT, Dillon MJ, Leonard JV (1991) Renal tubular dysfunction in methylmalonic acidaemia. Eur J Pediatr 150:259–263

    PubMed  Google Scholar 

  14. Walther JH, Michalski A, Wilson WM, Leonard JV, Barratt TM, Dillon MJ (1989) Chronic renal failure in methylmalonic acidaemia. Eur J Pediatr 148:344–348

    Google Scholar 

  15. Molteni KH, Oberley TD, Wolff JA, Friedman AL (1991) Progressive renal insufficiency in methylmalonic acidemia. Pediatr Nephrol 5:323–326

    CAS  PubMed  Google Scholar 

  16. Horster F, Hoffmann GF (2004) Pathophysiology, diagnosis and treatment of methylmalonic aciduria–recent advances and new challenges. Pediatr Nephrol 19:1071–1074

    PubMed  Google Scholar 

  17. Schmitt CP, Mehls O, Trefz FK, Horster F, Weber TL, Koller S (2004) Reversible end-stage renal disease in an adolescent patient with methylmalonic aciduria. Pediatr Nephrol 19:1182–1184

    PubMed  Google Scholar 

  18. Van’t Hoff W, McKiernan PJ, Surtees RAH, Leonard JV (1999) Liver transplantation for methylmalonic acidemia. Eur J Pediatr 158:S70–S74

    PubMed  Google Scholar 

  19. Meyburg J, Hoffmann GF (2005) Liver transplantation for inborn errors of metabolism. Transplantation 80:S135–S137

    PubMed  Google Scholar 

  20. Lubrano R, Scoppi P, Travasso E, Scateni S, Cristaldi S, Castello MA (2001) Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure. Pediatr Nephrol 16:848–851

    CAS  PubMed  Google Scholar 

  21. Giorgio AJ, Plaut GWE (1965) A method for the colorimetric determination of urinary MMA in pernicious anemia. J Lab Clin Med 66:667–676

    CAS  PubMed  Google Scholar 

  22. Heindreich R, Natowicz M, Hainline BE, Berman P, Kelli RI, Hillman RE, Berry GT (1988) Acute extrapyramidal syndrome in methylmalonic acidemia: “ metabolic stroke” involving the globus pallidus. J Pediatr 113:1022–1027

    Google Scholar 

  23. Hass RH, Marsden DL, Capistrano-Estrada S, Hamilton R, Grafe MR, Wong W, Nyhan WL (1995) Acute basal ganglia infarction in propionic acidemia. J Child Neurol 10:18–22

    Google Scholar 

  24. Davidson AN, Thompson RHS (1981) The molecular basis of neuropathology. Edward Arnold Limited, London, pp 104–131

    Google Scholar 

  25. Kolker S, Schwab M, Horster F, Sauer S, Hinz A, Wolf NI, Mayatepek E, Hoffmann GF, Smeitink JAM, Okun JG (2003) Methylmalonic acid, a biochemical hallmark of methylmalonic acidurias but no inhibitor of mitochondrial respiratory chain. J Biol Chem 278:47388–47393

    PubMed  Google Scholar 

  26. Pettenuzzo LF, Ferreira GC, Schmidt AL, Dutra-Filho CS, Wyse ATS, Wajner M (2006) Differential inhibitory effects of methylmalonic acid on respiratory chain complex activities in rat tissues. Int J Dev Neuroscience 24:45–52

    CAS  Google Scholar 

  27. Rotig A, Goutieres F, Niaudet P, Rustin P, Chretien D, Guest G, Mikol J, Gubler MC, Munnich A (1995) Deletion of mitochondrial DNA in patient with chronic tubulointerstitial nephritis. J Pediatr 126:567–601

    Google Scholar 

  28. Buemi M, Allegra A, Rotig A, Gubler MC, Aloisis C, Corica F, Pettinato G, Frisina N, Niaudet P (1997) Renal failure from mitochondrial cytopathies. Nephron 76:249–253

    CAS  PubMed  Google Scholar 

  29. Kashtan CE, Abousedira M, Rozen S, Manivel JC, McCann M, Tuchman M (1998) Chronich administration of methylmalonic acid (MMA) to rats causes proteinuria and renal tubular injury. Pediatr Res 43:309A

    Google Scholar 

  30. Chakrapani A, Sivakumar P, McKiernan PL, Leonard JV (2002) Metabolic stroke in methylmalonic acidemia five years after liver transplantation. J Pediatr 140:261–263

    PubMed  Google Scholar 

  31. Nyhan WL, Gargus JJ, Boyle K, Selby R, Koch R (2002) Progressive neurological disability in methylmalonic acidemia despite transplantation of the liver. Eur J Pediatr 161:377–379

    PubMed  Google Scholar 

  32. Kayler LK, Merion RM, Lee S, Sung RS, Punch JD, Rudich SM, Turcotte JG, Campbell DA Jr, Holmes R, Magee JC (2002) Long term survival after liver transplantation in children with metabolic disorders. Pediatr Transplant 6:295–300

    PubMed  Google Scholar 

  33. Hsui JY, Chein YH, Chu SY, Lu FL, Chen HL, Ho MJ, Lee PH, Hwu WL (2003) Living-related liver transplantation for methylmalonic academia: report of one case. Acta Paediatr Taiwan 44:171–173

    PubMed  Google Scholar 

  34. Huang HP, Chien YH, Huang LM, Ni YH, Chang MH, Ho MC, Lee PH, Hwu WL (2005) Viral infection and prolonged fever after liver transplantation in young children with inborn errors of metabolism. J Formos Med Assoc 104:623–629

    PubMed  Google Scholar 

  35. Morioka D, Kasahara M, Takada Y, Corrales JP, Yoshizawa A, Sakamoto S, Taira K, Yoshitoshi EY, Egawa H, Shimada H, Tanaka K (2005) Living donor liver transplantation for pediatric patients with inheritable metabolic disorders. Am J Transplant 5:2754–2763

    PubMed  Google Scholar 

  36. Kasahara M, Horikawa R, Tagawa M, Uemoto S, Yokoyama S, Shibata YT, Kawano T, Kuroda T, Honna T, Tanaka K, Saeki M (2006) Current role of liver transplantation for methylmalonic acidemia: a review of the literature. Pediatr Transplant 10:943–947

    PubMed  Google Scholar 

  37. Kaplan P, Ficicioglu C, Mazur AT, Palmieri MJ, Berry GT (2006) Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency. Mol Genet Metab 88:322–326

    CAS  PubMed  Google Scholar 

  38. Van’t Hoff WG, McKiernan PJ, Surtees RA, Leonard JV (1998) Combined liver-kidney transplantation in methylmalonic acidemia. J Pediatr 132:1043–1044

    Google Scholar 

  39. Nagarajan S, Enns GM, Millan MT, Winter S, Sarwal MM (2005) Management of methylmalonic acidaema by combined liver-kidney transplantation. J Inherit Metab Dis 28:517–524

    CAS  PubMed  Google Scholar 

  40. Coman D, Huang J, McTaggart S, Sakamoto O, Ohura T, McGill J, Burke J (2006) Renal transplantation in a 14-year-old girl with vitamin B12-responsive cnIA-type methylmalonic acidaemia. Pediatr Nephrol 21:270–273

    CAS  PubMed  Google Scholar 

  41. Van Calcar SC, Harding CO, Lyne P, Hogan K, Banerjee R, Sollinger H, Rieselbach RE, Wolff JA (1998) Renal transplantation in a patient with methylmalonic acidaemia. J Inher Metab Dis 21:729–737

    PubMed  Google Scholar 

  42. Andrews E, Jansen R, Crane AM, Cholin S, McDonnel D, Ledley F (1993) Expression of recombinant human methylmalonyl CoA mutase: in primary mut fibroblasts and Saccharomyces cerevisiae. Biochem Med Metab Biol 50:135–144

    CAS  PubMed  Google Scholar 

  43. Magera MJ, Helgeson JK, Matern D, Rinaldo P (2000) Methylmalonic acid measured in plasma and urine by stable-isotope dilution and electrospray tandem mass spectrometry. Clin Chem 46:1804–1810

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Pediatria, Università degli Studi di Roma “La Sapienza”, Viale Regina Elena 324, 00161, Rome, Italy

    Riccardo Lubrano, Elisabetta Travasso & Claudia Raggi

  2. Dipartimento di Scienze Cliniche “Osp. Luigi Sacco”, Università degli Studi di Milano, Via G.B. Grassi 74, 20157, Milan, Italy

    Marco Elli

  3. Dipartimento Chirugia Generale e Trapianti “Paride Stefanini”, Università degli Studi di Roma “la Sapienza”, Viale del Policlinico, 00161, Rome, Italy

    Massimo Rossi & Pasquale Berloco

  4. Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi di Roma “La Sapienza”, Rome, Italy

    Paola Barsotti & Claudia Carducci

Authors
  1. Riccardo Lubrano
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  2. Marco Elli
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  3. Massimo Rossi
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  4. Elisabetta Travasso
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  8. Pasquale Berloco
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Correspondence to Riccardo Lubrano.

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The study was made possible by an unrestricted grant from nuovArmonia nonprofit organization.

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Lubrano, R., Elli, M., Rossi, M. et al. Renal transplant in methylmalonic acidemia: could it be the best option?. Pediatr Nephrol 22, 1209–1214 (2007). https://doi.org/10.1007/s00467-007-0460-z

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  • DOI: https://doi.org/10.1007/s00467-007-0460-z

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