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Journal of Inherited Metabolic Disease

, Volume 35, Issue 5, pp 797–806 | Cite as

Metabolic decompensation in methylmalonic aciduria: which biochemical parameters are discriminative?

  • Tamaris Zwickler
  • Gisela Haege
  • Alina  Riderer
  • Friederike Hörster
  • Georg F. Hoffmann
  • Peter Burgard
  • Stefan Kölker
Original Article

Abstract

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.

Keywords

Uric Acid Base Excess Emergency Treatment Tricarboxylic Acid Cycle Base Balance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ALT

alanine aminotransferase

cblA

methylmalonic aciduria cblA type OMIM 251100

cblB

methylmalonic aciduria cblB type OMIM 251110

cblD

methylmalonic aciduria and homocystinuria cblD type, OMIM 277410

GFR

glomerular filtration rate

MCM

methylmalonyl-CoA mutase EC 5.4.99.2

MMA

methylmalonic acid

MMAuria

methylmalonic aciduria

mut0

complete defect of methylmalonyl-CoA-mutase activity OMIM 251000

mut-

partial defect of methylmalonyl-CoA-mutase activity OMIM 251000

Notes

Acknowledgement

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.

Supplementary material

10545_2011_9426_MOESM1_ESM.doc (72 kb)
Supplementary Table 1 (DOC 72.0 kb)
10545_2011_9426_MOESM2_ESM.doc (108 kb)
Supplementary Table 2 (DOC 108 kb)

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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • Tamaris Zwickler
    • 1
  • Gisela Haege
    • 1
  • Alina  Riderer
    • 1
  • Friederike Hörster
    • 1
  • Georg F. Hoffmann
    • 1
  • Peter Burgard
    • 1
  • Stefan Kölker
    • 1
  1. 1.Department of General Pediatrics, Division of Inherited Metabolic DiseasesUniversity Children’s Hospital HeidelbergHeidelbergGermany

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