To the Editor
We present a case of a nine-year-old male with cystic fibrosis, who
underwent hepato-portoenterostomy for biliary dysplasia and jejunal
resection for distal intestinal obstruction syndrome, requiring chronic
parenteral nutritional support. He required multiple transfusions for
episodes of severe anemia and thrombocytopenia and was referred to
hematology for further evaluation. At initial visit he had macrocytic
anemia (hemoglobin 7.3, reference range 11.5 - 13.5 g/dL; and mean
corpuscular volume [MCV] 96.1, (reference range 75-87 fl), mild
leukopenia (white blood cell count [WBC] 4.02, reference range 6.0
– 17.0 thou/uL) and severe neutropenia (absolute neutrophil count
[ANC] 0.442, reference range 0.72 - 7.525 thou/uL). While no
thrombocytopenia at visit, platelet counts previously ranged from 43 to
148 (reference range 150 - 450 thou/uL). On physical exam, significant
findings were short stature at less than fifteenth percentile for
height, pallor, mild hepatosplenomegaly and lower extremity weakness
Evaluation for his pancytopenia included Coombs and anti-neutrophil
antibody as destructive etiologies, which were both negative. Given
concern for nutritional deficiency, folate, vitamin B12, methylmalonic
acid, and vitamin E levels were obtained in addition to ferritin, serum
iron, saturation %, total iron binding capacity and soluble transferrin
receptor, which were all unremarkable. There were no significant
morphologic abnormalities noted on peripheral blood smear. With
unrevealing laboratory evaluation and in the context of his mild
organomegaly, anemia and thrombocytopenia were attributed to
hypersplenism. Due to persistent pancytopenia, notably WBC 1.31 thou/uL,
hemoglobin 5.8 g/dL, MCV 94.9 fl, platelet count 116 thou/uL and ANC
0.168 thou/uL, a bone marrow aspirate and biopsy evaluation was pursued.
While there was progressive myelopoiesis and no dysplastic features, his
marrow showed findings of vacuolated granules and ring sideroblasts,
which were suggestive of possible copper deficiency (Figure 1 ).
His serum copper level was very low at less than 5 mcg/dL (reference
range 117-181 mcg/dL) and serum ceruloplasmin level was less than 3
mg/dL (reference range 25-52 mg/dL, for males 7-9 years). The patient
was diagnosed with severe copper deficiency and replacement therapy with
daily enteral copper gluconate 2 mg was initiated.
Poor absorption from underlying cystic fibrosis complicated by
intestinal resection were primary contributors to the patient’s copper
deficiency. Additionally, prolonged parenteral nutrition and prior zinc
supplementation may have compounded his deficiency, related to zinc’s
antagonistic relationship to copper metabolism and
absorption.1 Two months following initiation of
enteral supplementation, his serum copper and ceruloplasmin levels
normalized. With ongoing supplementation, he had remarkable and
sustained improvement of his blood counts including hemoglobin ranging
from 11.7 to 14.8 g/dL, normalized MCV, WBC of 4.01 to 8.09 thou/uL,
improvement in ANC ranging from 1.620 to 5.20 thou/uL as well as
maintenance of a platelet count between 77 and 181 thou/uL.
In conclusion, our patient highlights the importance of assessment for
copper deficiency in a patient presenting with pancytopenia, especially
those with risk factors such as poor intestinal absorption or chronic
parenteral nutrition. Our patient had a remarkable count recovery
quickly following initiation of copper supplementation with no further
transfusion needs.