Hepatic copper in siblings of children with ICC.
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Biomedical subjects
Publications and source records attributed to S A Bhave.
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Brass and copper household utensils are a possible source of the gross hepatic copper accumulation characteristic of Indian childhood cirrhosis (ICC). In 107 families with a child with ICC, the use of copper or brass for water storage (97%) and of brass for milk storage (90%) or milk boiling (67%) resembled that of neighbouring village control families. However, the feeding history of 132 children with ICC differed from that of 70 children with other hepatic disorders and 311 children in 2 rural control groups. No child with ICC was exclusively breast-fed whereas 10%, 32%, and 25% of the control children were. Duration of breast-feeding was shorter in children with ICC and animal milk was introduced earlier. 57% were started on animal milk before 3 months of age. The age at introduction of animal milk correlated with the age at presentation with ICC. 66 urban Pune children had a feeding history similar to those with ICC, but in these families brass vessels were not used for milk. Experimentally, milk took up copper from utensils more avidly than water did. The copper concentration in milk samples obtained from ICC households, and those obtained experimentally, would supply a copper intake 6 to 20 times greater than that of the breast-fed infant, and similar to that producing copper toxicosis in the lamb. The hypothesis that early introduction of copper contaminated animal milk is of aetiological importance explains many of the epidemiological features of ICC.
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One hundred and twenty-five children with chronic liver disease were seen in Pune in 13 months. Fifty-nine of them, aged 8-39 months, had Indian childhood cirrhosis histologically diagnosed. Their characteristics included an insidious onset of symptoms, a geographical clustering of cases in rural areas north-east of Pune, a high rate of parental consanguinity and affected siblings, and a very high hepatic copper concentration (790-6654 micrograms/g dry weight). Only 8 survived for 6 months, adverse prognostic features being jaundice, ascites, enlargement of the gall bladder, and severe anaemia at presentation. Clinical differentiation from other liver disorders in the same age group was clear in advanced cases but unreliable in earlier cases. Four asymptomatic siblings with hepatomegaly had a benign course. The need for non-invasive methods to diagnose early cases in the community is demonstrated. The other major diagnostic categories were: unresolved hepatitis (12); chronic active hepatitis (7); cryptogenic cirrhosis (6); neonatal hepatitis and biliary atresia (8).
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One hundred prospectively studied children with Indian childhood cirrhosis (ICC) in Pune District, India, differed from 100 matched controls with respect to feeding history. Animal milk was used in all ICC cases but not in 27 controls. It had been started by 3 months in 63 cases and by 6 months in 82 cases of ICC, as compared with 15 and 25 controls. Twenty-four ICC cases received no breast feeding, and 45 and 60 were breast fed for less than 3 and less than 6 months, respectively; only 10 control children were breast fed for less than 6 months. All ICC children's feeds had been in contact with brass vessels. Copper vessels were used for water carriage with equal frequency in cases and controls. Girls predominated amongst healthy older siblings of cases. Ninety-one healthy siblings of cases had been fed similarly to controls. Three pairs of twins with similar feeding histories died with ICC, whereas two pairs were discordant for feeding and outcome. Hepatic copper loading in ICC is attributable to copper contamination of early animal milk feeds.