Copper deficiency masquerading as myelodysplastic syndrome

Gregg, Xylina; Reddy, Vishnu; Prchal, Josef T.

doi:10.1182/blood-2002-01-0256

Cited by 209 publications

(154 citation statements)

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“…Cop T a b l e 1 . P a t i e n t s ' L a b o r a r o r y P a r a me t e r s a n d t h e Re q u i r e d Do s e s o f Re c o mb i n a n t Hu ma n E r y t hr o p o i e t i n b e f o r e a n d a f t e r T h r e e Mo n t h s o f Co p p e r S u p p l e me n t a t i o n (9), and the low activity of copper-dependent enzymes such as ceruloplasmin ferroxidase and cytochrome oxidase, has been hypothesized to be a potential cause of anemia (10). Mitochondria isolated from copper-deficient animals were lacking in cytochrome oxidase activity and failed to synthesize heme from ferric iron and protoporphyrin at the normal rate, perhaps leading to mitochondrial iron accumulation (11).…”

Section: Introductionmentioning

confidence: 99%

Correction of Copper Deficiency Improves Erythropoietin Unresponsiveness in Hemodialysis Patients with Anemia

et al. 2006

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We have encountered five hemodialysis patients who had received enteral nutrition and recovered from erythropoietin-resistant anemia with neutropenia after the correction of copper deficiency. We reduced the required doses of recombinant human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is involved in erythropoietin-resistant anemia in hemodialysis patients.

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Section: Introductionmentioning

confidence: 99%

Correction of Copper Deficiency Improves Erythropoietin Unresponsiveness in Hemodialysis Patients with Anemia

et al. 2006

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“…Sideroblastic changes and nuclear maturation defects causing anemia and neutropenia have been observed in erythroid precursors of patients with copper deficiency. 1,14 A peripheral smear often reveals sideroblastic anemia with hypochromic microcytic red cells. Granulocyte levels can become very low, whereas platelet counts remain normal.…”

Section: Discussionmentioning

confidence: 99%

Copper Deficiency as Cause of Unexplained Hematologic and Neurologic Deficits in Patient with Prior Gastrointestinal Surgery

Ricker

Muench

2006

The Journal of the American Board of Family Medicine

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Copper is a trace mineral essential to hematopoiesis and to the structure and function of the nervous system. Copper deficiency is a rare cause of anemia, leukopenia, and myeloneuropathy, but should be considered in the differential diagnosis in a patient with prior gastrointestinal surgery. We report the case of a 51-year-old woman admitted for nonspecific neurologic symptoms ultimately found to be due to copper malabsorption. Case ReportsA 51-year-old female presented to the emergency department complaining of numbness and tingling in her distal lower extremities that had progressively worsened over the previous 4 weeks and had begun to affect her fingers 2 days before presentation. In addition, the patient stated that over the past 2 weeks she had experienced a progressively worsening shortness of breath, generalized weakness, fast heartbeat, and light-headedness.She had undergone a gastrectomy 16 years ago with Roux-en-Y and partial small bowel resection for treatment of Zollinger-Ellison syndrome as well as a Whipple procedure for chronic pancreatitis. Since her surgeries, she received vitamin B12 supplementation intramuscularly and was converted to oral supplementation several months before her presentation in the emergency department.On presentation, the patient's vital signs included a temperature of 36.7°C, blood pressure of 121/84, pulse of 80, respiratory rate of 18, oxygen saturation of 100% on room air, and weight of 43.2 kg. Initial neurological evaluation revealed diminished sensitivity to light touch and vibration and decreased proprioception in her toes and ankles. Her Babinski's reflex was positive bilaterally, and her Romberg was strongly positive. Her patellar and brachioradialis deep tendon reflexes were hyperreflexic bilaterally, but Achilles tendon reflexes were normal. Her cranial nerves were intact, and her sensation of pain and temperature were normal. Her motor strength was normal, but she had significant difficulty walking because of her sensory deficits. The physical examination was otherwise unremarkable.Laboratory tests in the emergency department included a hematocrit of 17% (normal range, 33% to 44.6%) with a mean corpuscular volume (MCV) of 105.9 fL (normal range, 80 to 96 fL). At this point, the patient was admitted for management of anemia and further evaluation of neurologic symptoms. She received a transfusion of 2 units of packed red blood cells, which brought her hematocrit up to 27%. She was also started on 100 mcg of vitamin B12 intramuscularly daily and 1 mg of folate orally daily.The patient's neurological and laboratory findings were initially attributed to vitamin B12 or folate deficiency, given her history of gastrointestinal surgery and recent conversion to oral vitamin B12 supplementation. However, her vitamin B12 and folate levels were available by the third day of hospitalization, with a vitamin B12 level of 738 pg/mL (normal range, 200 to 950 pg/mL) and folate level greater than 24 ng/mL (normal level, Ͼ0.9 ng/mL). Methylmalonic acid was 0.77 mol/L (normal lev...

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“…A rarely noted finding is the presence of prominent hemosiderin in plasma cells. 26 The majority of patients showed an improvement in their CBC or a complete hematologic response following either therapy with copper supplements or by eliminating excess dietary zinc or zinc supplements. [10][11][12] Multiple reports have implicated low copper levels in the pathogenesis of selected cases of refractory anemia with ringed sideroblasts (RARS) responsive to copper; all cases had normal platelet counts.…”

confidence: 99%

Hypocupremia and bone marrow failure

et al. 2008

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Hypocupremia and bone marrow failureCopper deficiency associated with neurological disorders is a well-documented condition. However, hypocupremia is less often recognized as a cause of cytopenias or bone marrow failure. We report an illustrative series of three new cases of bi-lineage cytopenia associated with copper deficiency. We have analyzed clinical features of current and historical cases to identify clues that could facilitate application of appropriate laboratory testing and heighten the level of clinical suspicion. By maintaining an appropriately high level of suspicion for potential copper deficiency and obtaining a serum copper level, bone marrow failure due to this condition can be correctly diagnosed and treated. We suggest that copper deficiency be included in the differential diagnosis of reversible causes of bone marrow failure syndromes including myelodysplastic syndrome. 93:e1-e5 DOI: 10.3324/haematol.12121 IntroductionIn the evaluation of patients with pancytopenia, reversible causes of bone marrow failure such as nutritional deficiencies, viral infections, and medications need to be considered in the differential diagnosis. Copper deficiency can be easily treated but the diagnosis may be difficult due to comorbidities and low level of clinical suspicion.Patients with copper deficiency most commonly present with neurological disorders, including myeloneuropathy, arthralgias and neuropathy. [1][2][3][4] A diagnosis of copper deficiency is usually established by measuring serum copper or ceruloplasmin levels; a serum copper level <10 ∝mol/L or ceruloplasmin <180 mg/L is considered presumptive evidence of copper deficiency. The most common hematologic abnormalities associated with copper deficiency include anemia and neutropenia, while the platelet count usually remains normal.The adult diet in Western countries contains 0.6 to 1.6 mg of copper/d. Water, shellfish, organ meats, nuts, and grains are all sources of dietary copper. Absorption occurs through the intestinal mucosa across the basement membrane into the blood stream via energy dependent mechanisms where the availability and saturation of copper may limit absorption. Of significant interest is the physiologic relationship between copper and zinc. High zinc levels result in increased metallothionin production in enterocytes. The high affinity of copper to metallothionin displaces zinc and thus leads to the accumulation of copper in the enterocytes. The enterocytes are ultimately shed into the gastrointestinal tract, leading to copper elimination. 5 Copper plays a role as a cofactor for many enzymes, in electron-transporting proteins, and in antioxidant metabolism. The main copper-binding protein is ceruloplasmin which plays a role in copper transport and release and in protection of cells from oxidative damage. Both ferroxidase and ceruloplasmin may oxidize Fe 2+ to Fe 3+ facilitating the release of Fe from ferritin and its binding to transferrin. 6 Copper is required for a variety of enzymes, including amino oxidase, ferroxidase, c...

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Copper deficiency masquerading as myelodysplastic syndrome

Cited by 209 publications

References 13 publications

Correction of Copper Deficiency Improves Erythropoietin Unresponsiveness in Hemodialysis Patients with Anemia

Correction of Copper Deficiency Improves Erythropoietin Unresponsiveness in Hemodialysis Patients with Anemia

Copper Deficiency as Cause of Unexplained Hematologic and Neurologic Deficits in Patient with Prior Gastrointestinal Surgery

Hypocupremia and bone marrow failure

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