The Syndrome of Neonatal Copper Deficiency

Abstract

A syndrome of primary copper deficiency in a 6-month-old premature baby is described. Features which can be ascribed to lack of copper, include (1) a sideroblastic anemia resistant to other therapy, with vacuolation of erythroid and myeloid bone marrow cells, and iron deposition in the vacuoles and in some mitochondria; (2) neutropenia, especially segmentopenia, which was common and prominent; (3) long-bone changes on radiological examination, particularly osteoporosis with blurring and cupping of the metaphyses; (4) depigmentation of skin and hair, with distended blood vessels due to changes in the elastin of the vessel walls; and (5) central nervous system abnormalities including hypotonia, psychomotor retardation, and difficulties with sight. Besides this small premature infant, who had received a relatively copper-deficient milk diet for at least three months, a second case has been seen in a 2,100-gm premature infant, after three months of intravenous alimenation necessitated by neonatal bowel surgery. Treatment with oral copper, 1 to 3 mg/day, dramatically cured both patients. It is recommended that 100 to 500µg/day of copper be added to the diet of small premature infants until they are receiving other foods beside milk, and to prolonged intravenous alimentation beginning in the newborn period.

Nutrient Transport in the Mammary Gland: Calcium, Trace Minerals and Water Soluble Vitamins

“…In this model, iron is finally secreted into milk by exocytosis of secretory vesicles at the apical membrane. The molecular entity that mediates iron oxidation after its transport by FPN remains unknown vulnerable to nutritional copper deficiency [127,128]. Moreover, toxic-milk (tx) mice pups die in the second week from severe copper deficiency due to low liver copper stores and low intakes from maternal copper-deficient milk [129].…”

Copper Deficiency in Infants with Active Celiac Disease

“…Hypocupremia is encountered in Menkes's disease and in the early stages of Wilson's disease, two rare inherited disorders affecting copper metabolism. Copper deficiency due to particularly high needs [prematurity (7,8) and recovery from severe PEM (9)(10)(11)(12)] or to very low intakes [non-copper-supplemented longterm total parenteral nutrition (13,14) and exclusive feeding with milk or milk-based formulas poor in copper (9,10,(14)(15)(16)(17)] has been documented. Finally, a few cases of hypocupremia have been reported in subjects with malabsorption due to long-lasting enteropathies (18)(19)(20).…”

“…The peripheral blood neutrophil count was the most sensitive parameter of copper depletion (15,(25)(26)(27). The initial absence of neutropenia in patient 1 could have been due to infection .…”

Relationship between copper and immunity: The potential role of copper in tumor immunity

“…The recommended daily dietary requirement of copper for a healthy adult is 0.9 mg. Copper is absorbed mainly through the small intestine, enters the liver through the portal vein and is partially excreted through the bile and mostly transported to different tissues and organs by binding to albumin and ceruloplasmin in the blood ( 3 ). In the 1950s, researchers found that copper deficiency causes hypocopperemia, hypoceruloplasminemia and neutropenia in infants ( 4 , 6 , 46 – 48 ) ( Figure 1 ). Following this, it was found that copper deficiency leads to impaired superoxide anion production by neutrophils, which kills bacteria ( 5 ).…”