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.