Thread by @fernandbteich

1/ What trace element deficiency can cause a syndrome similar to vitamin B12 deficiency? #BroadenYourDifferentials #MedTwitter

2/ It is indeed Copper deficiency! A.k.a. hypocupremia.

3/ Copper deficiency can cause a syndrome which includes variable combinations of anemia, leukopenia and/or neuromyelitis. Both the peripheral (neuropathy) and central (myelitis w/ features similar to subacute combined degeneration) nervous systems can be involved.

4/ Evaluation of bone marrow (in case of bicytopenia or pancytopenia) may reveal MDS-like changes leading to an erroneous diagnosis. Note, for instance, the dysplastic bi-lobed megakaryocyte in the picture below (courtesy of Forrest et. al).

4/ Who's at risk? Patients with:
- Malnutrition
- Impaired absorption (celiac disease, IBD, etc)
- Excess zinc consumption (can cause both iron and copper deficiency). Contained in lozenges to treat cold
- Bariatric surgery
- Menkes disease (congenital, STEP1 memory)

5/ When suspected (and initial B12 level is normal), low levels of copper and ceruloplasmin in the serum are consistent with diagnosis of deficiency. Confirmation with a low 24-hour urine copper level.
These tests are, however, not perfect: bmj.com/content/348/bm…

6/ Treat the underlying cause (stop zinc supplementation, correct cause of malabsorption).
Treat with oral copper (2-8 mg of elemental copper daily). Cytopenias can recover rapidly but neurologic manifestations may not improve despite supplementation.

7/ Further reading and a great clinical reasoning case:
Vallurupalli, M., Divakaran, S., Parnes, A., Levy, B. D., & Loscalzo, J. (2019). The Element of Surprise. New England Journal of Medicine, 381(14), 1365–1371.
nejm.org/doi/full/10.10…