Our report adds new findings to the current existing literature of various other cytogenetic abnormalities seen in the bone marrow from severe B12 deficiency. the importance to exclude B12 deficiency in patients with new diagnosis of myelodysplasia with cytogenetic abnormalities. Case presentation A 38-year-old African-American woman was initially referred to our haematology medical center for evaluation of macrocytic anaemia. The patient was in a normal state of health until 6?months prior to this presentation. She then experienced progressively worsening fatigue, heart burn, nocturnal cough and excess weight loss over 20?lbs. Relevant physical examination and vital indicators were grossly unremarkable. Initial laboratory findings were as follows: haemoglobin (Hb): 10?g/dL, mean corpuscular volume: 110?fL, white cell count (WCC): 3.92103/L, platelets: 281?000/L, reticulocyte count: 1.4%, serum B12: 4187?pg/mL, serum folate: 33?ng/mL, iron: 84?g/dL, total iron binding capacity: 251?g/dL, G15 ferritin: 119?ng/mL, transferrin saturation: 33%, lactate dehydrogenase: 205?U/L, haptoglobin: 32?mg/dL, thyroid stimulating hormone: DGKH 0.650?IU/mL, copper: 166?g/dL. Hepatitis and Human Immunodeficiency Computer virus 1 and 2 serology was unfavorable. Peripheral blood smear revealed macrocytosis, anisocytosis, tear drop cells, adequate platelets and no evidence of dysplastic cells. Secondary to peripheral blood examination exposing macrocytic red blood cells, tear drop cells in the context of normal B12 levels, a bone marrow biopsy was suggested, which was declined by the patient. Six months later after being lost to follow-up, she presented to the emergency room with bilateral lower leg weakness and her physical examination revealed marked skin hyperpigmentation, glossitis, moderately increased muscular tone, decreased sensation to touch and pressure in the lower extremities, decreased reflexes in the ankle and knee joints and wide based gait. Investigations Repeat laboratory findings were: Hb: 8.6?g/dL, WCC: 2.06103/L, platelets: 193?000/L, folate: 19.9?ng/mL. Bone marrow biopsy revealed hypercellular bone marrow with megaloblastic and dysplastic changes, 6% CD34+ blast cells and rare ringed sideroblasts. Metaphase cytogenetic studies on bone marrow aspirate showed del 20?q (physique 1). B12 this time was noted to be at 83?pg/mL, serum homocysteine: 218?mol/L, serum methyl malonic acid: 23246?nmol/L. Antiparietal antibody and anti-intrinsic factor antibody were strongly positive. The initial obtaining of a falsely elevated B12 levels can be perceived as an erroneous laboratory finding. Open in a separate window Physique?1 This determine demonstrates cytogenetic analysis revealing 20 q deletion before vitamin B12 replacement (chromosome 20 magnified (not to scale) to demonstrate the abnormality). Differential G15 diagnosis At patient’s initial presentation, as all the work up for macrocytic anaemia was unfavorable, myelodysplasia was considered in the differential diagnosis. But, the differential diagnosis was soon narrowed to B12 deficiency when the patient presented later with severe ataxia along with classic neurological manifestations in the presence of macrocytic anaemia. The primary diagnosis of pernicious anemia was confirmed when the serology was positive for both anti-parietal and anti-intrinsic factor antibodies. Treatment The patient was subsequently treated with intramuscular B12 supplementation (1000?g every day for 1?week, every 1?week for 4?weeks and G15 month to month thereafter) with rapid resolution of all haematological parameters in a week and more gradual improvement of neurological symptoms. End result and follow-up Seventy days after B12 replacement, a repeat bone marrow biopsy was performed and revealed a normocellular bone marrow with no evidence of myelodysplastic features and 3% CD34+ blast cells. Repeat cytogenetic studies on bone marrow aspirate exhibited normal female karyotype and reversal of prior noted del 20q (physique 2). Open in a separate window Physique?2 This physique demonstrates normal female karyotype and the reversal of the previously seen 20 q deletion after vitamin B12 replacement. Conversation Dietary B12 (cobalamin) is usually assimilated in the distal ileum after binding to intrinsic factor secreted by the gastric parietal cells.1 Cobalamin aids in the conversion of 5-methyl tetrahydrofolate (THF) to N 5,10 methylene THF, which is necessary for deoxy-thymidine monophosphate (dTMP) synthesis.2 Cobalamin also mediates the conversion of homocysteine to methionine which is a precursor for S-adenosyl methionine, a methyl donor required for the maintenance of methylation patterns in DNA and the synthesis of formyl-THF.2 Deficiency of B12 also prospects to accumulation of homocysteine. B12 deficiency ultimately prospects to trapping of folate, increased deoxy-uridine monophosphate (dUMP), which prevents incorporation of dTMP into the DNA. High intracellular ratio of dUMP/dTMP and subsequent increase in the deoxy-uridine triphosphate/deoxy-thymidine triphosphate (dUTP/dTTP) ratio results in misincorporation of uracil into the DNA strand.3C5.