Copper Deficiency Presenting With Bicytopenia During Long-Term Parenteral Nutrition for Short Bowel Syndrome: A Case Report and Literature Review

The patient was a 24-year-old female with pyruvate dehydrogenase complex deficiency and cerebral palsy. At 14 years of age, she developed short bowel syndrome due to intestinal obstruction and began receiving total parenteral nutrition (TPN) at home. At 15 years of age, the patient developed intestinal failure associated with liver disease. At 23 years of age, she rapidly developed jaundice and liver dysfunction. Liver biopsy revealed significant iron deposition, which led to the discontinuation of trace element supplementation. She was referred to our department 10 months after the discontinuation of trace element supplementation because of bicytopenia (Hb 5.7 g/dL and neutrophils 1,363/μL). During the course of the illness, the neutrophil count dropped to 204/μL. Although she had macrocytic anemia (MCV 101.0 fl), no decrease in vitamin B12 or folate levels was observed. Copper was decreased to 4 μg/dL (reference range: 80-155 μg/dL), and ceruloplasmin was ≤2 mg/dL (reference range: 20-40 mg/dL). Bone marrow examination revealed hyperplastic marrow with dysplasia in the erythroid lineage and cytoplasmic vacuolation in both the erythroid and granulocytic lineages, but no increase in blasts and a normal karyotype. Anemia due to zinc deficiency typically presents as normocytic or microcytic anemia. Based on the macrocytic anemia and characteristic bone marrow findings, copper deficiency was considered the cause of the hematopoietic disorder; therefore, trace element supplementation was resumed. After red blood cell transfusion and the initiation of trace element supplementation, an increase in copper levels was confirmed; anemia improved on the fourth day and remained stable, while neutrophil counts recovered within two weeks. This case was considered to be a result of copper deficiency due to multiple factors, including malabsorption due to short bowel syndrome, long-term TPN administration, and discontinuation of trace element supplementation, leading to hematopoietic dysfunction. Recently, deficiencies in trace elements such as zinc and selenium during parenteral nutrition have been highlighted, and attention to copper deficiency is also warranted. Regular monitoring and careful dose adjustments are essential in children at high risk of trace element deficiency. Furthermore, cytopenia caused by copper deficiency may require differentiation from myelodysplastic syndrome based on bone marrow findings. However, because hematologic recovery is typically promptly observed with copper supplementation, accurate diagnosis and treatment are crucial.