Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient

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Background: Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods: Comprehensive data on patient’s vitamin B12, eGFR and MMA concentrations were collected (n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results: Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90–300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions: Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.

Original languageEnglish
Pages (from-to)685-692
Number of pages8
JournalAnnals of Clinical Biochemistry
Issue number6
Publication statusPublished - 1 Nov 2018


  • data mining
  • decision support
  • methylmalonic acid
  • personalized laboratory medicine
  • renal failure
  • Vitamin B
  • Biostatistics
  • Vitamin B 12/blood
  • Humans
  • Middle Aged
  • Male
  • Methylmalonic Acid/chemistry
  • Female
  • Retrospective Studies
  • ErbB Receptors/chemistry
  • Vitamin B 12 Deficiency/diagnosis


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