Copper deficiency
Copper deficiency, or hypocupremia, is defined as insufficient copper to meet the body's needs, or as a serum copper level below the normal range. Symptoms may include fatigue, decreased red blood cells, early greying of the hair, and neurological problems presenting as numbness, tingling, muscle weakness, and ataxia. The neurodegenerative syndrome of copper deficiency has been recognized for some time in ruminant animals, in which it is commonly known as "swayback". Copper deficiency can manifest in parallel with vitamin B12 and other nutritional deficiencies.
Overview
The most common cause of copper deficiency is a remote gastrointestinal surgery, such as gastric bypass surgery, due to malabsorption of copper, or zinc toxicity. On the other hand, Menkes disease is a genetic disorder of copper deficiency involving a wide variety of symptoms that is often fatal.Copper is required for the functioning of many enzymes, such as cytochrome c oxidase, which is complex IV in the mitochondrial electron transport chain, ceruloplasmin, Cu/Zn superoxide dismutase, and in amine oxidases. These enzymes catalyze reactions for oxidative phosphorylation, iron transportation, antioxidant and free radical scavenging and neutralization, and neurotransmitter synthesis, respectively. Diets vary in the amount of copper they contain, but may provide about 5 mg/day, of which only 20-50% is absorbed. The diet of the elderly may have a lower copper content than the recommended daily intake. Dietary copper can be found in whole grain cereals, legumes, oysters, organ meats, cherries, dark chocolate, fruits, leafy green vegetables, nuts, poultry, prunes, and soybean products like tofu.
Copper deficiency can have many hematological consequences, such as myelodysplasia, anemia, low white blood cell count, and low count of neutrophils.
Signs and symptoms
Blood symptoms
The characteristic hematological effects of copper deficiency are anemia and neutropenia. Thrombocytopenia is unusual.The peripheral blood and bone marrow aspirate findings in copper deficiency can mimic myelodysplastic syndrome. Bone marrow aspirate in both conditions may show dysplasia of blood cell precursors and the presence of ring sideroblasts. 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 patient's paraesthesias did resolve. Since this discovery, awareness of copper-deficiency myelopathy and its treatment has increased. Patients typically present difficulty walking caused by sensory ataxia due to dorsal column dysfunction or degeneration of the spinal cord. 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. T2 signalling is often an indicator of neurodegeneration. There are some changes in the spinal cord MRI involving the thoracic cord, the cervical cord, or sometimes both. Copper deficiency myelopathy is often compared to subacute combined degeneration. Subacute combined degeneration is also a degeneration of the spinal cord, but instead vitamin B12 deficiency is the cause of the spinal degeneration. SCD also has the same high T2 signalling intensities in the posterior column as copper deficient patient in MRI imaging.
Peripheral neuropathy
Another common symptom of copper deficiency is peripheral neuropathy, which is numbness or tingling that can start in the extremities and can sometimes progress radially inward towards the torso. In an Advances in Clinical Neuroscience & Rehabilitation published case report, a 69-year-old patient had progressively worsened neurological symptoms. These symptoms included diminished upper limb reflexes with abnormal lower limb reflexes, sensation to light touch and pin prick was diminished above the waist, vibration sensation was lost in the sternum, and markedly reduced proprioception or sensation about the self's orientation. Many people with the neurological effects of copper deficiency complain about very similar or identical symptoms as the patient. This numbness and tingling pose a danger for the elderly because it increases their risk of falling and injuring themselves. Peripheral neuropathy can become very disabling leaving some patients reliant on wheelchairs or walking canes for mobility if there is a lack of correct diagnosis. Rarely can copper deficiency cause major disabling symptoms. The deficiency must be present for an extensive amount of time until such disabling conditions manifest.Optic neuropathy
Some patients with copper deficiency have shown signs of vision and color loss. The vision is usually lost in the peripheral views of the eye. The bilateral vision loss is usually very gradual. An optical coherence tomography shows some nerve fiber layer loss in most patients, suggesting the vision loss and color vision loss was secondary to optic neuropathy or neurodegeneration.Causes
Surgery
is a common cause of copper deficiency. Bariatric surgery, such as gastric bypass surgery, is often used for weight control of the morbidly obese. The disruption of the intestines and stomach from the surgery can cause absorption difficulties not only as regards copper but also for iron and vitamin B12 and many other nutrients. The symptoms of copper deficiency myelopathy may take up to decades to develop.Zinc toxicity
Increased zinc consumption is another cause of copper deficiency. Zinc is often used for the prevention or treatment of common colds and sinusitis, ulcers, sickle cell disease, celiac disease, memory impairment, and acne. Zinc is found in many common vitamin supplements and is also found in denture creams. Recently, several cases of copper deficiency myeloneuropathy were found to be caused by prolonged use of denture creams containing high quantities of zinc.Metallic zinc is the core of all United States currency coins, including copper-coated pennies. People who ingest many 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
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 has a wide variety of symptoms including floppy muscle tone, seizures, abnormally low body temperature, and a peculiar steel color hair that feels very rough. Menkes disease is usually fatal, with the majority of affected 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.