Tag Archives: methylmalonic acid

Methylmalonic Acid as a Biomarker of Vitamin B12

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A recent case study (L Jimenez et al. J Pediatr 2018; 192: 259-61) showed that methylamalonic acid (MMA) can be elevated in the absence of vitamin B12 deficiency.

Background:

  • Risk factors for vitamin B12 deficiency: terminal ileal resection and gastric acid blockade
  • Manifestations of vitamin B12 deficiency: megaloblastic anemia, bone marrow failure, demyelinating diseases, thrombosis, and psychiatric symptoms
  • Early assessment of vitamin B12 deficiency can be aided by MMA levels and homocysteine levels both of which are metabolized via vitamin B12-dependent pathways and are elevated in vitamin B12 deficiency.
  • MMA levels have higher sensitivity for vitamin B12 deficiency than vitamin B12 levels alone.

Key findings of this report:

  • In three children with short bowel syndrome, MMA levels were persistently elevated despite vitamin B12 supplementation and without other evidence of vitamin B12 deficiency
  • MMA levels declined after treatment of bacterial overgrowth
  • “It is hypothesized that propionate, a precursor to MMA, produced by excessive gut fermentation, is responsible for the elevation in plasma MMA levels.”

My take: this study is a good reminder of how MMA is useful in detecting vitamin B12 deficiency and points out that bacterial overgrowth may be an alternative explanation for elevated MMA levels.

Related blog posts:

Resources for Short Bowel Syndrome:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Bright Angel Trail, Grand Canyon

Are we missing Vitamin B12?

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This is the question that I wonder after reading a recent review (NEJM 2013; 368: 149-60) -especially since effective treatment is readily available.

While vitamin B12 deficiency is most common in individuals 70 to 80 years, it affects all age groups.  A particularly vulnerable group are infants of mothers with vitamin B12 deficiency.  These infants may be born with deficiency or it may develop if exclusively breast-fed, usually between 4 and 6 months of age.  Indications of this deficiency include failure of brain development, poor growth, hypotonia, and feeding difficulties.  Some infants develop tremors, lethargy, and hyperirritability.  Imaging may show atrophy and delayed myelination.

Mothers who are at most risk:

  • unrecognized pernicious anemia
  • history of gastric bypass
  • short gut syndrome
  • long-term vegetarian or vegan diet

Other pediatric conditions that cause B12 deficiency: ileal resections, Imerslund-Grasbeck syndrome (Imerslund–Gräsbeck syndrome (selective vitamin B12 malabsorption ..), inflammatory bowel disease, and pernicious anemia.

Other Key Points from this review:

  • B12 deficiency causes reversible megaloblastic anemia, demyelinating neurologic disease or both
  • B12 deficiency is the major cause of hyperhomocysteinemia in countries with folate-fortified food and contributes to a risk of vascular disease and thrombosis
  • Autoimmune gastritis (pernicious anemia) is the most common cause of severe deficiency (in adults).  Tests to determine underlying reason for B12 deficiency include the following: anti-intrinsic factor antibodies (must be checked off treatment for at least 7 days), anti-parietal cell antibodies -both help detect pernicious anemia, gastrin level (high level) & pepsinogen I (low levels) both suggestive of atrophic gastritis.  The Schilling test of radioactive B12 is no longer available.  Endoscopy is frequently performed in adults with B12 deficiency.
  • Methylmalonic acid (MMA) is the best indicator for untreated B12 deficiency; MMA >400 nmol/L has 98% sensitivity for B12 deficiency.  Other causes of increased MMA include renal failure and volume depletion.
  • Serum B12 has poor sensitivity and specificity -though performs adequately at higher cut-off value (<350pg/mL has 90% sensitivity)
  • Many individuals require lifelong treatment with either parenteral B12 or high-dose oral tablets (see article for dosing recommendations)

Additional references:

  • -J Pediatr 2010; 157: 162.  B12 deficiency in newborns –especially if mother has had bariatric surgery or vegan diet.
  • -J Pediatr 2001; 138: 10 (review) At risk for deficiency: strict veggie, abnl absorption (gastric resection, pernicious anemia), long term PPI, bacterial overgrowth, ileal disruption (Crohn’s), or ileal receptor d/o (Imersund-Grasbeck),  inborn B12 metabolism d/o

Clinical Sx: FTT, weakness, anorexia, neuro/psych sx, macrocytic anemia, pancytopenia, glossitis, vomit/diarrhea

Dx: low vit B12, incr methylmalonic acid & incr homocysteine.  MMA specific for B12; homocysteine incr also if folate deficient.

If Vit B12 deficient, reason for this needs to be determined.