Response to a Letter to the Editor Entitled “Low Serum B12 Level Does Not Mean Vit. B12 Deficiency-Problems Related to the Diagnosis of Vitamin B12 Deficiency”

We thank Dr Grzybowski1 for the interest he has shown in our article entitled “Evaluation of peripapillary retinal nerve fiber layer thickness in patients with vitamin B12 deficiency using spectral domain optical coherence tomography”.2

Firstly, Dr Grzybowski argues that low serum vitamin B12 level is not automatically diagnostic for vitamin B12 deficiency in asymptomatic, hematologically normal patients. He states that the clinical picture is crucial for determination of the vitamin B12 deficiency. In addition, he says that the levels of the other biomarkers such as methylmalonic acid or homocysteine could be used for the diagnosis. In our study, we used serum vitamin B12 levels, clinico-electrophysiological evaluation and spinal magnetic resonance imaging for the diagnosis of vitamin B12 deficiency and related neuropathies. Eight patients had clinical vitamin B12 deficiency. However, the rest of the patients (37 patients) had subclinical cobalamin deficiency (SCCD). They were hematologically normal patients and they had no clinical signs except for the low serum vitamin B12 levels. It is known that the anemia is not seen in the SCCD.3 Biochemical markers of cobalamin status have largely confirmatory roles in the diagnosis of clinical deficiency of vitamin B12, whose clinical expressions provide the diagnostic quasi-gold standard.3 Cobalamin measurement is generally sufficient for the diagnosis because it has more than 90–95% sensitivity in the clinical deficiency.4,5 On the other hand, the diagnosis of SCCD depends completely on metabolic testing because the patients are clinically normal. However, the optimal testing for diagnosis of SCCD continues to be investigated.3 As recently reported, all biomarkers can produce falsely abnormal results, and none is a diagnostic gold standard.3,5

Secondly, Dr Grzybowski points out that the reason for vitamin B12 deficiency in our patients was not given and intrinsic factor (IF)-related malabsorption was not verified. The cause of vitamin B12 deficiency and IF was not evaluated in our work because it has been shown that the causes of SCCD are unknown in more than 60% of cases.3

As Dr Grzybowski states, there are some problems with the diagnosis of vitamin B12 diagnosis. He has enriched our article by discussing these problems throughout his letter. We, sincerely thank him for his contribution to our work.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.