Introduction: Copper deficiency (hypocupremia) is a rare nutritional deficiency. Like a myelodysplastic syndrome (MDS), it may present with cytopenias and macrocytosis, or may mimic B12/folate deficiency with neurological symptoms. Bone marrow features of vacuolated erythroid and myeloid precursors should raise the suspicion of copper deficiency. Patients at risk for hypocupremia include those with dietary deficiencies and/or malabsorption, including a subgroup who have undergone bariatric surgery.
Methods: Two cases of hypocupremia were reviewed. Peripheral blood and bone marrow films stained with May-Grunwald -Giemsa were examined in conjunction with clinical notes.
Results:
Case 1: 35/F (G1P0 38+3) with gastric bypass (Roux-en-Y, 2004) presented with lower limb swelling, macrocytic anaemia (Hb:75g/L. MCV:110fL), a leucoerythroblastic blood film and neurological symptoms. Although mildly hypertensive, a fulminant HELLP syndrome was unlikely as no erythroid fragmentation was seen. A low copper level was noted at 6.8umol/L (Ref: 12-22umol/L), with normal B12/folate levels. This was consistent with nutritional deficiency exacerbated by pregnancy demands. IV copper was administered with recovery of the anaemia, resolution of the macrocytosis and symptomatic improvement.
Case 2: 23/M with autism presented with extreme fatigue in conjunction with a pancytopenia (Hb:72g/L, platelets:32x109/L, neutrophils:0.5x x109/L), low serum folate (4.1nmol/L) but normal serum B12. Progressive bloods showed occasional blasts triggering bone marrow evaluation. Megaloblastic erythroid changes were noted consistent with folate deficiency. However, additional changes not typically associated with megaloblastosis were noted including atypical megakaryocytes with frequent nuclear separation and some small hypolobulated forms; hypogranulated giant metamyelocytes and granulocytes. The cytopenias persisted despite cessation of valproate. Nutritional deficiency was suspected as the patient had an extremely selective diet. Copper levels were found to be low 10umol/L (Ref: 12-22umol/L) with normal zinc levels. The full blood count normalised only after the commencement of oral supplements and reestablishment of normal copper levels.
Conclusions: Hypocupremia is a rare dietary deficiency with haematological ramifications; including macrocytosis, anaemia and/or cytopenias; and is a described mimicker of other serious disorders. Although vacuolation of bone marrow precursors are noted, this unusual feature is not entirely unique to copper deficiency alone. Thus the diagnosis of hypocupraemia should be considered in patient’s nutritional deficiency or malabsorption, particularly those with a history of gastric surgery. Cop per replacement therapy is a simple and effective measure to completely reverse these features.