To the Editor
We present a nine-year-old boy with cystic fibrosis, biliary dysplasia corrected with hepato-portoenterostomy, and distal intestinal obstruction syndrome resulting in jejunal resection with intermittent cytopenias since two years of age. Namely, a macrocytic anemia with mean corpuscular volume (MCV) 87–109 fL, leukopenia below 3 thou/uL, neutropenia 0.035–0.705 thou/uL and mild to moderate thrombocytopenia of 48–147 thou/uL. He had frequent episodes of culture-negative sepsis syndrome requiring intensive care stays ever 2-3 months, during which he required frequent transfusions with packed red cells, often once hemoglobin reached below 7 g/dL, as well as intermittent platelet transfusions.
Our patient presented to general hematology with pancytopenia at 3 years. Initial evaluation included negative Coombs and anti-neutrophil antibody with normal folate, vitamin B12, methylmalonic acid (MMA), vitamin E, iron studies and soluble transferrin receptor. Peripheral smear revealed no morphologic abnormalities. His physical exam was notable for pallor, lower extremity weakness and mild hepatosplenomegaly. Initially, anemia and thrombocytopenia were attributed to hypersplenism; however, with persistent pancytopenia, bone marrow evaluation was performed. Marrow studies showed progressive myelopoiesis without evidence of dysplasia or malignancy, but the presence of vacuolated granulocytic and erythroid precursors and ring sideroblasts prompted evaluation of a potential copper deficiency. A serum copper level of <5 (reference range 117-181 mcg/dL) and serum ceruloplasmin level of <3 (reference range for male 7-9 is 25-52 mg/dL) confirmed his severe copper deficiency.
Our patient’s copper deficiency was attributed to poor absorption secondary to his cystic fibrosis and gut resection. In addition, prior zinc supplementation, used to promote growth in CF, was thought to compound deficiency due to zinc’s interference with copper metabolism.1 After two months of enteral supplementation with copper gluconate at 2 mg daily, serum copper and ceruloplasmin levels normalized (Figure 1 ). There was significant improvement in hematological parameters: normalization of hemoglobin, MCV, WBCs and neutrophils, and as stabilization of his platelet count (Figure 1 ). Given his response, supplementation was suspended for some time; however, later resumed upon recurrence of pancytopenia.