An expanding spectrum of complications in isolated methylmalonic aciduria

Forny, Patrick; Grunewald, Stephanie

doi:10.34763/jmotherandchild.20202402si.2014.000003

Abstract

Isolated methylmalonic acidurias represent a heterogeneous genetic group of inborn errors of propionate metabolism with the common biochemical hallmark of elevated methylmalonic acid present in tissues and body fluids. It was first described in the 1960s and over the years better understanding of the disease and its presentation, earlier diagnosis, and most importantly advances in treatment have resulted in extended survival of patients. With that an expanding spectrum of complications is emerging which requires attention and regular monitoring to facilitate early intervention and reduce disease burden.

References

Fowler B, Leonard JV, Baumgartner MR. Causes of and diagnostic approach to methylmalonic acidurias. J Inherit Metab Dis. 2008;31(3):350–60. doi:10.1007/s10545-008-0839-4.
Open DOI Search in Google Scholar Back to article
Froese DS, Fowler B, Baumgartner MR. Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis. 2019;42(4):673–85. doi:10.1002/jimd.12009.
Open DOI Search in Google Scholar Back to article
Hörster F, Garbade SF, Zwickler T, Aydin HI, Bodamer OA, Burlina AB, et al. Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters. J Inherit Metab Dis. 2009;32(5):630. doi:10.1007/s10545-009-1189-6. Epub 2009 Jul 31. Erratum in: J Inherit Metab Dis. 2009;32(6):762–3.
Open DOI Search in Google Scholar Back to article
Kölker S, Garcia-Cazorla A, Valayannopoulos V, Lund AM, Burlina AB, Sykut-Cegielska J, et al. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015;38(6):1041–57. doi:10.1007/s10545-015-9839-3. Erratum in: J Inherit Metab Dis. 2015;38(6):1155–6. Cazorla, Angeles Garcia [corrected to Garcia-Cazorla, Angeles].
Open DOI Search in Google Scholar Back to article
Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014;9:130. doi:10.1186/s13023-014-0130-8.
Open DOI Search in Google Scholar Back to article
Oberholzer VG, Levin B, Burgess EA, Young WF. Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis. Arch Dis Child. 1967;42(225):492–504. doi:10.1136/adc.42.225.492.
Open DOI Search in Google Scholar Back to article
Hörster F, Baumgartner MR, Viardot C, Suormala T, Burgard P, Fowler B, et al. Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB). Pediatr Res. 2007;62(2):225–30. doi:10.1203/PDR.0b013e3180a0325f.
Open DOI Search in Google Scholar Back to article
Kölker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, et al. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015;38(6):1059–74. doi:10.1007/s10545-015-9840-x. Erratum in: J Inherit Metab Dis. 2015;38(6):1157–8. Garcia Cazorla, Angeles [corrected to Garcia-Cazorla, Angeles].
Open DOI Search in Google Scholar Back to article
Haijes HA, Jans JJM, Tas SY, Verhoeven-Duif NM, van Hasselt PM. Pathophysiology of propionic and methylmalonic acidemias. Part 1: complications. J Inherit Metab Dis. 2019;42(5):730–44. doi:10.1002/jimd.12129.
Open DOI Search in Google Scholar Back to article
Kruszka PS, Manoli I, Sloan JL, Kopp JB, Venditti CP. Renal growth in isolated methylmalonic acidemia. Genet Med. 2013;15(12):990–6. doi:10.1038/gim.2013.42.
Open DOI Search in Google Scholar Back to article
Cosson MA, Benoist JF, Touati G, Déchaux M, Royer N, Grandin L, et al. Long-term outcome in methylmalonic aciduria: a series of 30 French patients. Mol Genet Metab. 2009;97(3):172–8. doi:10.1016/j.ymgme.2009.03.006.
Open DOI Search in Google Scholar Back to article
Noone D, Riedl M, Atkison P, Avitzur Y, Sharma AP, Filler G, et al. Kidney disease and organ transplantation in methylmalonic acidaemia. Pediatr Transplant. 2019;23(4):e13407. doi:10.1111/petr.13407.
Open DOI Search in Google Scholar Back to article
Luciani A, Schumann A, Berquez M, Chen Z, Nieri D, Failli M, et al. Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. Nat Commun. 2020;11(1):970. doi:10.1038/s41467-020-14729-8. Erratum in: Nat Commun. 2020;11(1):1719. 10.1038/s41467-020-15565-6.
Open DOI Search in Google Scholar Back to article
de Keyzer Y, Valayannopoulos V, Benoist JF, Batteux F, Lacaille F, Hubert L, et al. Multiple OXPHOS deficiency in the liver, kidney, heart, and skeletal muscle of patients with methylmalonic aciduria and propionic aciduria. Pediatr Res. 2009;66(1):91–5. doi:10.1203/PDR.0b013e3181a7c270.
Open DOI Search in Google Scholar Back to article
Manoli I, Sysol JR, Li L, Houillier P, Garone C, Wang C, et al. Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia. Proc Natl Acad Sci U S A. 2013;110(33):13552–7. doi:10.1073/pnas.1302764110.
Open DOI Search in Google Scholar Back to article
Haarmann A, Mayr M, Kölker S, Baumgartner ER, Schnierda J, Hopfer H, et al. Renal involvement in a patient with cobalamin A type (cblA) methylmalonic aciduria: a 42-year follow-up. Mol Genet Metab. 2013;110(4):472–6. doi:10.1016/j.ymg-me.2013.08.021.
Open DOI Search in Google Scholar Back to article
Prada CE, Al Jasmi F, Kirk EP, Hopp M, Jones O, Leslie ND, et al. Cardiac disease in methylmalonic acidemia. J Pediatr. 2011;159(5):862-864. doi:10.1016/j.jpeds.2011.06.005.
Open DOI Search in Google Scholar Back to article
Vatanavicharn N, Champattanachai V, Liammongkolkul S, Sawangareetrakul P, Keeratichamroen S, Ketudat Cairns JR, et al. Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia. Mol Genet Metab. 2012;106(4):424–9. doi:10.1016/j.ymgme.2012.05.012.
Open DOI Search in Google Scholar Back to article
Ktena YP, Paul SM, Hauser NS, Sloan JL, Gropman A, Manoli I, et al. Delineating the spectrum of impairments, disabilities, and rehabilitation needs in methylmalonic acidemia (MMA). Am J Med Genet A. 2015;167A(9):2075–84. doi:10.1002/ajmg.a.37127.
Open DOI Search in Google Scholar Back to article
de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D, Saudubray JM. Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis. 2005;28(3):415–23. doi:10.1007/s10545-005-7056-1.
Open DOI Search in Google Scholar Back to article
Kahler SG, Millington DS, Cederbaum SD, Vargas J, Bond LD, Maltby DA, et al. Parenteral nutrition in propionic and methyl-malonic acidemia. J Pediatr. 1989;115(2):235–41. doi:10.1016/s0022-3476(89)80071-x.
Open DOI Search in Google Scholar Back to article
Marquard J, El Scheich T, Klee D, Schmitt M, Meissner T, Mayatepek E, et al. Chronic pancreatitis in branched-chain organic acidurias – a case of methylmalonic aciduria and an overview of the literature. Eur J Pediatr. 2011;170(2):241–5. doi:10.1007/s00431-010-1313-5.
Open DOI Search in Google Scholar Back to article
Thul PJ, Akesson L, Wiking M, Mahdessian D, Geladaki A, Blal H, et al. A subcellular map of the human proteome. Science (New York, N.Y.). 2017;356(6340):eaal3321. doi:10.1126/science. aal3321.
Open DOI Search in Google Scholar Back to article
Brassier A, Krug P, Lacaille F, Pontoizeau C, Krid S, Sissaoui S, et al. Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: the French experience. J Inherit Metab Dis. 2020;43(2):234–43. doi:10.1002/jimd.12174.
Open DOI Search in Google Scholar Back to article
Imbard A, Garcia Segarra N, Tardieu M, Broué P, Bouchereau J, Pichard S, et al. Long-term liver disease in methylmalonic and propionic acidemias. Mol Genet Metab. 2018;123(4):433–40. doi:10.1016/j.ymgme.2018.01.009.
Open DOI Search in Google Scholar Back to article
Forny P, Hochuli M, Rahman Y, Deheragoda M, Weber A, Baruteau J, et al. Liver neoplasms in methylmalonic aciduria: an emerging complication. J Inherit Metab Dis. 2019;42(5):793–802. doi:10.1002/jimd.12143.
Open DOI Search in Google Scholar Back to article
Cosson MA, Touati G, Lacaille F, Valayannnopoulos V, Guyot C, Guest G, et al. Liver hepatoblastoma and multiple OXPHOS deficiency in the follow-up of a patient with methylmalonic aciduria. Mol Genet Metab. 2008;95(1–2):107–9. doi:10.1016/j.ymg-me.2008.06.007.
Open DOI Search in Google Scholar Back to article
Chan R, Mascarenhas L, Boles RG, Kerkar N, Genyk Y, Venkatramani R. Hepatoblastoma in a patient with methylmalonic aciduria. Am J Med Genet A. 2015;167A(3):635–8. doi:10.1002/ajmg.a.36925.
Open DOI Search in Google Scholar Back to article
Nicolaides P, Leonard J, Surtees R. Neurological outcome of methylmalonic acidaemia. Arch Dis Child. 1998;78(6):508–12. doi:10.1136/adc.78.6.508.
Open DOI Search in Google Scholar Back to article
Martín-Hernández E, Lee PJ, Micciche A, Grunewald S, Lachmann RH. Long-term needs of adult patients with organic acidaemias: outcome and prognostic factors. J Inherit Metab Dis. 2009;32(4):523–33. doi:10.1007/s10545-009-1191-12.
Open DOI Search in Google Scholar Back to article
O’Shea CJ, Sloan JL, Wiggs EA, Pao M, Gropman A, Baker EH, et al. Neurocognitive phenotype of isolated methylmalonic acidemia. Pediatrics. 2012;129(6):e1541–51. doi:10.1542/peds.2011-1715.
Open DOI Search in Google Scholar Back to article
Wajner M. Neurological manifestations of organic acidurias. Nat Rev Neurol. 2019;15(5):253–71. doi:10.1038/s41582-019-0161-9.
Open DOI Search in Google Scholar Back to article
Pinar-Sueiro S, Martínez-Fernández R, Lage-Medina S, Al-damiz-Echevarria L, Vecino E. Optic neuropathy in methylmalonic acidemia: the role of neuroprotection. J Inherit Metab Dis. 2010;33(Suppl 3):S199–203. doi:10.1007/s10545-010-9084-8.
Open DOI Search in Google Scholar Back to article
Manoli I, Myles JG, Sloan JL, Shchelochkov OA, Venditti CP. A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias. Genet Med. 2016;18(4):386–95. doi:10.1038/gim.2015.102.
Open DOI Search in Google Scholar Back to article
van der Meer SB, Poggi F, Spada M, Bonnefont JP, Ogier H, Hubert P, et al. Clinical outcome and long-term management of 17 patients with propionic acidaemia. Eur J Pediatr. 1996;155(3):205–10. doi:10.1007/BF01953939.
Open DOI Search in Google Scholar Back to article
Yannicelli S, Acosta PB, Velazquez A, Bock HG, Marriage B, Kurczynski TW, et al. Improved growth and nutrition status in children with methylmalonic or propionic acidemia fed an elemental medical food. Mol Genet Metab. 2003;80(1–2):181–8. doi:10.1016/j. ymgme.2003.08.012.
Open DOI Search in Google Scholar Back to article
Molema F, Gleich F, Burgard P, van der Ploeg AT, Summar ML, Chapman KA, et al.; Additional individual contributors from E-IMD. Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders: on the basis of information from a European multicenter registry. J Inherit Metab Dis. 2019;42(6):1162–75. doi:10.1002/jimd.12066.
Open DOI Search in Google Scholar Back to article
Touati G, Valayannopoulos V, Mention K, de Lonlay P, Jouvet P, Depondt E, et al. Methylmalonic and propionic acidurias: management without or with a few supplements of specific amino acid mixture. J Inherit Metab Dis. 2006;29(2–3):288–98. doi:10.1007/s10545-006-0351-7.
Open DOI Search in Google Scholar Back to article
Diodato D, Olivieri G, Pro S, Maiorani D, Martinelli D, Deodato F, et al. Axonal peripheral neuropathy in propionic acidemia: a severe side effect of long-term metronidazole therapy. Neurology. 2018;91(12):565–7. doi:10.1212/WNL.0000000000006209.
Open DOI Search in Google Scholar Back to article
Goolsby TA, Jakeman B, Gaynes RP. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature. Int J Antimicrob Agents. 2018;51(3):319–25. doi:10.1016/j.ijantimicag.2017.08.033.
Open DOI Search in Google Scholar Back to article
Alston TA, Abeles RH. Enzymatic conversion of the antibiotic metronidazole to an analog of thiamine. Arch Biochem Biophys. 1987;257(2):357–62. doi:10.1016/0003-9861(87)90577-7.
Open DOI Search in Google Scholar Back to article
Kapoor K, Chandra M, Nag D, Paliwal JK, Gupta RC, Saxena RC. Evaluation of metronidazole toxicity: a prospective study. Int J Clin Pharmacol Res. 1999;19(3):83–8.
Search in Google Scholar Back to article
Forny P, Schumann A, Mustedanagic M, Mathis D, Wulf MA, Nägele N, et al. Novel mouse models of methylmalonic aciduria recapitulate phenotypic traits with a genetic dosage effect. J Biol Chem. 2016;291(39):20563–73. doi:10.1074/jbc. M116.747717.
Open DOI Search in Google Scholar Back to article
Lucienne M, Aguilar-Pimentel JA, Amarie OV, Becker L, Calzada-Wack J, da Silva-Buttkus P, et al. In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock- in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria. Biochim Biophys Acta Mol Basis Dis. 2020;1866(3):165622. doi:10.1016/j.bbadis.2019.165622.
Open DOI Search in Google Scholar Back to article

An expanding spectrum of complications in isolated methylmalonic aciduria

Abstract

Paradigm

My account