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A New Approach for Fast Metabolic Diagnostics in CMAMMA

  • Monique G. M. de Sain-van der VeldenEmail author
  • Maria van der Ham
  • Judith J. Jans
  • Gepke Visser
  • Hubertus C. M. T. Prinsen
  • Nanda M. Verhoeven-Duif
  • Koen L. I. van Gassen
  • Peter M. van Hasselt
Research Report
Part of the JIMD Reports book series (JIMD, volume 30)

Abstract

Background: The presence of increased urinary concentrations of both methylmalonic acid (MMA) and malonic acid (MA) is assumed to differentiate combined malonic and methylmalonic aciduria (CMAMMA), due to mutations in the ACSF3 gene, from other causes of methylmalonic aciduria (classic MMAemia). Detection of MA in urine, however, is challenging since excretion of MA can be easily missed. The objective of the study was to develop a method for quantification of MA in plasma to allow differentiation between CMAMMA and classic MMAemia.

Methods: Compound heterozygosity for mutations in the ACSF3 gene was detected in two female siblings using diagnostic exome sequencing. Urine (MMA and MA) was analyzed with GC/MS, while plasma was analyzed with UPLC-MS/MS. MA/MMA ratios were calculated.

Results: Both patients had a severe psychiatric presentation (at the age of 6 years and 5.5 years, respectively) after a viral infection. MA excretion in the patients was only just above the highest control value in several samples. MA concentrations in plasma from the two patients were clearly above the highest value observed in control subjects. However, MA concentrations in plasma from patients with classic MMAemia were also elevated. Additional, calculation of MA/MMA ratio in plasma allowed to fully differentiate between CMAMMA and classic MMAemia.

Conclusions: Calculating the MA/MMA ratio in plasma allows differentiation between CMAMMA and classic MMAemia. The full clinical spectrum of CMAMMA remains to be delineated.

Keywords

Malonic Acid Methylmalonic Acid Organic Acid Analysis Methylmalonic Aciduria 3MCC Deficiency 
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.

Notes

Acknowledgments

We like to thank Martina de Barse and Karen van Baal.

References

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Monique G. M. de Sain-van der Velden
    • 1
    Email author
  • Maria van der Ham
    • 1
  • Judith J. Jans
    • 1
  • Gepke Visser
    • 2
  • Hubertus C. M. T. Prinsen
    • 1
  • Nanda M. Verhoeven-Duif
    • 1
  • Koen L. I. van Gassen
    • 1
  • Peter M. van Hasselt
    • 2
  1. 1.Department of Medical GeneticsUMC UtrechtUtrechtThe Netherlands
  2. 2.Department of Pediatric Gastroenterology and Metabolic DiseasesUniversity Medical Centre (UMC) UtrechtUtrechtThe Netherlands

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