A literature review found two cases of copper deficiency myelopathy secondary to parenteral zinc supplementation during chronic dialysis.Metallic zinc is the core of all United States currency coins, including copper-coated pennies. People who ingest a large number of coins will have elevated zinc levels, leading to zinc-toxicity-induced copper deficiency and the associated neurological symptoms. This was the case for a 57-year-old woman diagnosed with schizophrenia. The woman consumed over 600 coins, and started to show neurological symptoms such as unsteady gait and mild ataxia. Hereditary disorders
Menkes disease is a congenital disease that is a cause of copper deficiency. Menkes disease is a hereditary condition caused by a defective gene involved with the metabolism of copper in the body. Menkes disease involves a wide variety of symptoms including floppy muscle tone, seizures, abnormally low temperatures, and a peculiar steel color hair that feels very rough. Menkes disease is usually a fatal disease with most children dying within the first ten years of life. Other
It is rarely suggested that excess iron supplementation causes copper deficiency myelopathy. Another rarer cause of copper deficiency is celiac disease, probably due to malabsorption in the intestines. Still, a large percentage, around 20%, of cases have unknown causes. Pathophysiology
Copper functions as a prosthetic group, which permits electron transfers in key enzymatic pathways like the electron transport chain. Copper is integrated in the enzymes cytochrome c oxidase, which is involved in cellular respiration and oxidative phosphorylation, Cu/Zn dismutase, which is involved in antioxidant defense, and many more listed in the table below.
Unlike most cases of myelodysplastic syndrome, the bone marrow aspirate in copper deficiency characteristically shows cytoplasmic vacuoles within red and white cell precursors, and karyotyping in cases of copper deficiency does not reveal cytogenetic features characteristic of myelodysplastic syndrome.Anemia and neutropenia typically resolve within six weeks of copper replacement. Neurological symptoms
Copper deficiency can cause a wide variety of neurological problems including myelopathy, peripheral neuropathy, and optic neuropathy. Myelopathy
Copper deficiency myelopathy in humans was discovered and first described by Schleper and Stuerenburg in 2001. They described a patient with a history of gastrectomy and partial colonic resection who presented with severe tetraparesis and painful paraesthesias and who was found on imaging to have dorsomedial cervical cord T2 hyperintensity. Upon further analysis, it was found that the patient had decreased levels of serum coeruloplasmin, serum copper, and CSF copper. The patient was treated with parenteral copper and the patients paraesthesias did resolve. Since this discovery, there has been heightened and increasing awareness of copper-deficiency myelopathy and its treatment, and this disorder has been reviewed by Kumar. Patients typically present difficulty walking (gait difficulty) caused by sensory ataxia (irregular muscle coordination) due to dorsal column dysfunction or degeneration of the spinal cord (myelopathy). Patients with ataxic gait have problems balancing and display an unstable wide walk. They often feel tremors in their torso, causing sideways jerks and lunges.In brain MRI, there is often an increased T2 signalling at the posterior columns of the spinal cord in patients with myelopathy caused by copper deficiency.