Vigorous periosteal reaction secondary to copper deficiency in an infant on total parenteral nutrition

Sir, We are using this forum to share our recent experience with a 5-month-old child who had dramatic radiographic findings, in order to alert health care workers, including pediatric radiologists, about the increased likelihood of seeing copper deficiency cases in view of the scarcity of parenteral copper. Depending on the supply available, parenteral copper has been frequently omitted from total parenteral nutrition formulations in the last year or so [1]. A 5-month-old boy was transferred to our hospital for intestinal rehabilitation and evaluation for possible intestinal transplantation. He had been born at a gestational age of 34 weeks secondary to preterm labor. Prenatal US was concerning for polyhydramnios and intestinal obstruction. At birth he was found to have multiple small bowel atresias. After multiple surgeries for resections with reanastomosis, he remained dependent on parenteral nutrition and intolerant of enteral feeds. The child had been hospitalized since birth. The original chest/abdomen radiograph at our hospital showed vigorous periosteal reaction of humeri and femurs (sparing the region of the metaphysis) (Fig. 1) along with periosteal reaction of some ribs and the scapulae. Our original differential diagnoses included diffuse osteomyelitis, hypertrophic pulmonary osteoarthropathy, scurvy, vitamin D deficiency and child abuse. A bone survey then revealed osteoporosis (for example, the zone of provisional calcification of knee secondary centers could be seen better than the bone inside) and multiple metaphyseal abnormalities appearing as spurs (Fig. 2) and similar in some locations to “bucket handle” classic metaphyseal lesions of child abuse (Fig. 3). The pattern was somewhat suggestive of scurvy, a disease rarely seen in current practice. The other diagnoses considered were Menkes syndrome (kinky hair syndrome) and copper deficiency from inadequate intake. Vitamin C levels were normal, eliminating scurvy as a diagnosis. Recognition of the national shortage of intravenous micronutrients and trace elements led to evaluation of intake of copper in this boy with intestinal failure who had been dependent on total parenteral nutrition his entire life. It was discovered that because of the national shortage of parenteral copper, he had not received any copper at the referring hospital. A serum copper level showed a very low level of <10 μg/dL (normal 75–165 μg/dL), a very low ceruloplasmin level <4 mg/dL (normal 18–37 mg/dL), and alkaline phosphatase of 1,324 IU/L (normal 82–383 IU/L). Vitamin D, calcium and phosphorus levels were normal. He was anemic (hemoglobin 8.3 g/dL) on admission with normal white blood cell count. In the absence of any enteral feeds and knowledge of absence of copper in the total parenteral nutrition, the radiologic changes were attributed to acquired copper deficiency. Radiologic findings in this boy are consistent with prior reports of profound infantile copper deficiency [2, 3]. The exuberant extent of the periosteal reaction may well relate to the many weeks of normal in-patient handling of the baby without realizing he was bleeding subperiosteally. Copper deficiency leads to reduction of the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the nervous system [4]. Children with deficient copper A. E. Oestreich (*) Department of Radiology, Cincinnati Children’s Hospital Medical Center Radiology 5031 CCHMC, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA e-mail: alan.oestreich@cchmc.org