His diarrhea subsided on Trimethoprim-Sulfamethoxazole and intravenous fluids with aggressive electrolyte repletion. However, the patient’s lower extremity weakness persisted. Physical examination was notable for 5/5 strength of the upper extremities and 3/5 strength of the lower extremities, with weakened (2/5) plantarflexion of the left foot. Initially, there was concern for steroid-induced myopathy, given the patient’s chronic use of Prednisone. Initial work up, including VDRL, HIV, HTLV-1/2, West Nile, Lyme titers, autoimmune serologies, and lumbar puncture were negative. MRI showed dorsal segment abnormality concerning for subacute combined degeneration of the cervical spine. Given the patient’s MRI findings, serum B12, folate, methylmalonic acid were checked, but all returned normal. Zinc (43, 56-134 ug/dL), copper (10, 72-166 ug/dL), homocysteine (4.5, 5-15 umol/L) and ceruloplasmin (4, 20-60 mg/dL) were, however, all abnormally low. His ataxia was attributed to hypocupremia, in the setting of chronic malabsorption from Isospora belli.
Discussion: Copper is a cofactor in several important mechanisms, including the electron transport chain anti-oxide defense. Absorption occurs in the stomach and proximal duodenum, therefore deficiency is often seen in patients with prior surgeries or malabsorption syndromes. Gastric acid solubilizes the copper, which is then bound to proteins and transported to the liver where it is incorporated into ceruloplasmin for cellular delivery. A normal Western diet provides adequate amounts of copper. Symptomatic hypocupremia in the United States is thus rare. Patients often present with sensory ataxias and imaging can show increased T2 MRI signal, particularly of the dorsal cervical spine. Treatment involves copper supplementation and cessation of excessive zinc intake—as zinc blocks copper uptake. There is no report of clinical reversal of neurological symptoms, but patients have reported subjective sensory improvement with effective copper supplementation.
Conclusions: While hypocupremia has been consistently linked to hematologic derangements, neurologic abnormalities, including subacute degeneration of the dorsal cervical spine, has emerged a salient manifestation of copper deficiency. Copper deficiency mimics B12 deficiency. Hypocupremia should, thus, be considered in patients presenting with intractable neurological deficits, where all other workup for infectious and autoimmune etiologies proves unrevealing.