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Previously, we mentioned how we would like to see the MMA test and the holoTC (“active-B12”) test used in combination to help diagnose B12 deficiency. To show real-life scenarios where measuring holoTC could help, we’d like to share some anecdotes and case reports from Axis-Shield Diagnostics, developers of the active-B12 test.
Active-B12 Case Studies
Haptocorrin Deficiency Leading to Low Total-B12
In the first case, patient showed total-B12 levels of 98 pmol/L and appeared to have a B12 deficiency. However, he had no clinical signs like anemia, neuropathy, macrocytosis, or high levels of homocysteine or MMA. An active-B12 test then revealed levels of 46 pmol/L, indicating that his true, bio-available B12 stores were likely replete.
Turns out, he had a partial deficiency of haptocorrin with no clinical consequences. His low total-B12 levels led to several follow-up tests, incurring added cost and hassle, whereas a single active-B12 test would have given a congruent result.
In a second case, a B12 deficiency was suspected in a 89-year-old patient. His total-B12 levels were low at 114 pmol/L. However, his holoTC was high, at 99 pmol/L. Like in the other case, it seems that his low total-B12 levels were due to a deficiency in haptocorrin, causing low holohaptocorrin (“inactive-B12”) levels. Dr. Ralph Carmel suggests that up to 15% of patients with low levels of B12 may have a mild haptocorrin deficiency.
Low Total-B12 During Pregnancy
In a third case, patient was 38 weeks pregnant and underwent tests for B12 deficiency after complaining of numbness. Total-B12 levels were 77 pmol/L, suggesting a lack of B12. Her doctor even suspected she has pernicious anemia, probably due to the disease’s history. However, an active-B12 test showed normal levels of 43 pmol/L.
In pregnancy, total-B12 levels drop, but it’s due to falling levels of holoHC (“inactive B12”). HoloTC (“active B12”) remains mostly unchanged. As her active-B12 test showed, the patient’s holoTC levels seemed normal. Her numbness may or may not have been related to her B12 levels, and an MMA test could help a lot here.
Hypothyroidism & B12 Deficiency
The fourth case shows an 87 year-old patient with shortness of breath and anemia. His hemoglobin was low, MCV was normal, and TSH was high – pointing to hypothyroidism. His total-B12 levels were 170 pmol/L, indicating sufficiency (by most hospitals, though not by us). Normal RBC folate and serum folate levels indicated that his iron status was normal and the anemia was presumed to be due to the hypothyroidism.
However, his holoTC (“active B12”) concentration was only 4 pmol/L, indicating a severe B12 deficiency. Hypothyroidism patients can have this discrepancy between total-B12 and holoTC levels. In this case, the active-B12 test would have saved time, revealing the severe deficiency immediately, allowing to start B12 treatment right away.
Hematological Disorders Confounding B12 Status
The fifth case brings a 87 year-old patient suffering from non-Hodgkin’s lymphoma. She was severely anemic, with high RDW and low MCV, indicating microcytosis. However, there was no reason to be microcytic, because ferritin levels were very high. Total-B12 levels were also high, at 373 pmol/L, so patient appeared to be B12-replete.
However, an active-B12 test revealed her severe B12 deficiency, at only 12 pmol/L. So even though her blood levels of total-B12 looked normal, she was totally deficient. Abnormalities in carrier proteins are evident in many hematological disorders, in this case affecting B12 transport and confounding the regular B12 blood test.
If you’re interested, you can read more about the holoTC test here. We don’t like calling it an active-B12 test, because transcobalamin can also bind to non-active cobalamins. But the test does have some merit, especially in combination with MMA.
Thank you for reading.