Volledig artikel van o.a. Dr. Bruce H.R. Wolffenbuttel (UMCG Groningen)
SPECIAL ARTICLE MAYO CLINIC PROCEEDINGS: INNOVATIONS, QUALITY & OUTCOMES
Mayo Clin Proc Inn Qual Out n June 2019;
Published online 2019 May 27.
Bruce H.R. Wolffenbuttel, MD, PhD, Hanneke J.C.M. Wouters, BSc, [...], and Melanie M. van der Klauw, MD, PhD
a Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
b Department of Haematology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
c Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
Bruce H.R. Wolffenbuttel: ln.gcmu@owb
The Many Faces of Cobalamin (Vitamin B12) Deficiency
Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult to
establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency
may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12
deficiency may present with the classic megaloblastic anemia.
In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even
misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with
vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated
biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical
symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical
signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and
The spectrum of symptoms and signs suggestive of vitamin B12 deficiency is reasonably well defined. Nevertheless, many of the symptoms are nonspecific and may occur as aconsequence of other diseases.
Currently, no research has documented the positive and negative predictive values of specific symptoms
or symptom scores for the presence of vitamin B12 deficiency.
Patients with low serum vitamin B12 levels may have no symptoms (yet). Nevertheless, they are at high risk for development of symptoms.
There is a tendency among physicians to consider a serum vitamin B12 level higher than 140 pmol/L as normal, but many symptomatic patients may present with such levels, for instance because of taking oral vitamin supplementation.
This does not mean that their tissue vitamin B12 levels are normal as well. Methylmalonic acid and homocysteine are not very sensitive biomarkers, but there is currently no good alternative, although systematic evaluation of more advanced metabolic factors may lead to the application of better biomarkers.
When serum total vitamin B12 levels are low or questionable, the combination of total vitamin B12, active vitamin B12, MMA, and homocysteine may be the best strategy, but the validity of this combined biomarker approach43
needs to be validated in larger prospective studies and especially validated against objective markers of treatment response.
In case of doubt, when results of biomarker measurements are equivocal, a trial with parenteral hydroxocobalamin injections may be considered, as was done in patients B and D.
Because symptom improvement in long-standing (subclinical) vitamin B12 deficiency may take some time, we usually advise a treatment regimen of twice weekly hydroxocobalamin injections for 3 months, after which a thorough reevaluation is performed with systematic evaluation of symptom score as demonstrated in patient B (Table 2).
There is no proof in large prospective, double-blind studies that oral supplementation is as effective in reducing symptoms associated with vitamin B12 deficiency as parenteral treatment.
Frequently Reported Misconceptions and Misbeliefs Regarding Vitamin B12 Deficiency
Self-Reported Symptoms of Patient B Before and 1 and 6 Months After Initiation of Hydroxocobalamin Therapy
Spectrum of Polyglandular Autoimmune Syndrome
https://www.ncbi.nlm.nih.gov/pmc/articl ... f/main.pdf