Metabolic decompensation in methylmalonic aciduria: which biochemical parameters are discriminative?
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Recurrent, life-threatening metabolic decompensations often occur in patients with methylmalonic aciduria (MMAuria). Our study evaluated (impending) metabolic decompensations in these patients aiming to identify the most frequent and reliable clinical and biochemical abnormalities that could be helpful for decision-making on when to start an emergency treatment. Seventy-six unscheduled and 179 regular visits of 10 patients with confirmed MMAuria continuously followed by our metabolic centre between 1975 and 2009 were analysed. The most frequent symptom of an impending acute metabolic decompensation was vomiting (90% of episodes), whereas symptoms of intercurrent infectious disease (29%) or other symptoms (such as food refusal and impaired consciousness) were found less often. Thirty-five biochemical parameters were included in the analysis. Among them, pathological changes of acid–base balance reflecting metabolic acidosis with partial respiratory compensation (decreased pH, pCO2, standard bicarbonate, and base excess) and elevated ammonia were the most reliable biochemical parameters for the identification of a metabolic decompensation and the estimation of its severity. In contrast, analyses of organic acids, acylcarnitines and carnitine status were less discriminative. In conclusion, careful history taking and identification of suspicious symptoms in combination with a small number of rapidly available biochemical parameters are helpful to differentiate compensated metabolic condition and (impending) metabolic crisis and to decide when to start an emergency treatment.
KeywordsUric Acid Base Excess Emergency Treatment Tricarboxylic Acid Cycle Base Balance
methylmalonic aciduria cblA type OMIM 251100
methylmalonic aciduria cblB type OMIM 251110
methylmalonic aciduria and homocystinuria cblD type, OMIM 277410
glomerular filtration rate
methylmalonyl-CoA mutase EC 184.108.40.206
complete defect of methylmalonyl-CoA-mutase activity OMIM 251000
partial defect of methylmalonyl-CoA-mutase activity OMIM 251000
This study is dedicated to the patients and their families whom the authors thank for their trust and kind cooperation. Special thanks to all colleagues who participated throughout the years caring for and providing information on their patients, notably M. Lindner, D. Haas, V. Konstantopoulou, H. Schmidt, A. Schulze and F. Trefz. We thank S. Körner for excellent technical assistance in programming the MS Access data base.
Details of Funding
The study is supported by the “Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen”. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
- Abdi H (2007) Bonferroni and Sidak corrections for multiple comparisons. In: Salkind NJ (ed) Encyclopedia of Measurement and Statistics. Sage, Thousand Oaks, pp 103–107Google Scholar
- Edgington ES (1995) Randomization tests, 3rd edn. Marcel-Dekker, New York, pp 1–409Google Scholar
- Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (2002) Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 417:447–452PubMedGoogle Scholar
- Fenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York, pp 2165–2193Google Scholar
- Howell DC (2001) Resampling Procedures Version 1.3. Retrieved from http://www.uvm.edu/~dhowell/StatPages/Resampling/ResamplingPackage.zip on November 9, 2010
- National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–S246Google Scholar
- Okun JG, Hörster F, Farkas LM, Feyh P, Hinz A, Sauer S, Hoffmann GF, Unsicker K, Mayatepek E, Kölker S (2002) Neurodegeneration in methylmalonic aciduria involves inhibition of complex II and the tricarboxylic acid cycle, and synergistically acting excitotoxicity. J Biol Chem 277:14674–14680PubMedGoogle Scholar
- Smucker MD, Allan J., Carterette B (2007) A comparison of statistical significance tests for information retrieval evaluation. Proceedings of the sixteenth ACM conference on Conference on Information and Knowledge Management (CIKM). November 05–10, 2007, Lisbon, Portugal. ACM, New York, pp 623–632Google Scholar