Low Serum Copper Concentrations Research Articles

B-165 Establishment of a Labile Bound Copper and Labile Bound Copper Ratio Reference Interval in a Healthy Adult Population

Abstract Background While clinical tests are available to aid in the diagnosis of Wilson’s Disease (WD), some such as total copper determination lack sensitivity and specificity, while others such as liver tissue copper assessment are costly and invasive. WD affects copper metabolism and is known to cause low serum copper concentrations. In addition, an elevated percentage of total serum copper exists as non-protein bound or labile bound copper (LBC). Previous studies have shown that measuring the ratio of labile bound copper to total serum copper may aid in the diagnosis of WD. To support the utility of a laboratory developed test using serum LBC ratios to aid in the diagnosis of WD, serum samples from healthy donors were used to establish a reference range for LBC and the ratio of LBC to total copper in adults. Methods Serum samples were collected in trace metal free tubes from 214 donors (n = 110 male, n = 104 female) between the ages of 19–80 years old, selected against pre-determined exclusion criteria including acute hepatitis, chronic hepatitis, renal failure, biliary cirrhosis, celiac disease, and leukemia. Prior to analysis, samples went through a centrifugation-based preparation process to isolate the LBC fraction using molecular weight size exclusion filters and EDTA chelation. Samples were then analyzed via ICP-MS in kinetic energy discrimination (KED) mode to directly measure the LBC and total copper concentrations. LBC ratio values were determined from the LBC/total copper concentrations. Results Preliminary reference ranges were developed for both LBC and the LBC ratio based on the 2.5th and 97.5th percentiles with 95% confidence intervals. Established sex specific reference intervals for total copper were deemed acceptable per CLSI guidelines in document EP28-A3c, with ≤10% of results from this sample set falling outside of the established intervals. No statistically significant relationship was found in the mid-95th percentile between LBC concentration or ratio with age or sex. The reference intervals for LBC concentration were calculated as 13.41–104.66 and 11.69–106.50 ng/mL for females and males respectively. The reference intervals for LBC ratio were calculated as 1.04–8.12 and 1.17–10.48 for females and males respectively. Conclusions A reference range of LBC and LBC ratio has now been determined for the healthy adult population. Further testing can now be done on disease state populations to determine the sensitivity and specificity of LBC ratio in the detection, monitoring, or diagnosis of WD.

Iatrogenic Copper Deficiency: Risks and Cautions with Zinc Prescribing.

Copper deficiency resulting from prescribing zinc in high doses is a rare but life-changing diagnosis that is frequently overlooked. The aim of this study is to gauge how often zinc-induced copper deficiency is missed, to raise awareness of the condition and to stress the need for guidelines for prescribing zinc. Suspected cases of zinc-induced copper deficiency were retrospectively obtained by selecting those patients with hyperzincaemia and hypocupraemia from the database of the Scottish Trace Element Laboratory. Case records were reviewed to determine the validity of the suspected diagnosis. After exclusions, 23 instances of high serum zinc and low serum copper concentrations were found. A positive diagnosis of zinc-induced copper deficiency was made in 14 patients of which 7 (50%) were previously undiagnosed. Serum zinc and copper concentrations are rarely measured in patients prescribed zinc and so the vast majority of cases of zinc-induced copper deficiency are likely to be undiagnosed. We recommend the current official advice on the dose and frequency of zinc administration is revised in order to limit, and potentially eradicate, the condition.

Wilson’s Disease with Late Hepatic Involvement

Wilson’s Disease (WD) is an autosomal recessive condition that affects copper metabolism and manifests itself clinically in different ways. The diagnosis is indicated by low serum copper and ceruloplasmin concentrations, increased urine copper excretion and/ or increased hepatic copper concentrations. The present case report is about a 55-year-old male with chief complaints of loss of appetite, abdominal swelling, tremors in hand and head, slurring of speech for 10 days. Ultrasound (USG) findings were suggestive of liver cirrhosis with portal hypertension and liver function tests were also deranged. He was prescribed diuretics and asked to review after 10 days. Kayser-Fleischer ring was observed through slit lamp examination in both the eyes, which is a hallmark of WD. The Magnetic Resonance Imaging (MRI) of brain also revealed positive findings-hyperintensity throughout the mesencephalon for WD. Thereafter, the patient was treated with penicillamine and his symptoms improved after few days

Abnormal concentrations of acetylated amino acids in cerebrospinal fluid in acetyl-CoA transporter deficiency.

Acetyl-CoA transporter 1 (AT-1) is a transmembrane protein which regulates influx of acetyl-CoA from the cytosol to the lumen of the endoplasmic reticulum and is therefore important for the posttranslational modification of numerous proteins. Pathological variants in the SLC33A1 gene coding for AT-1 have been linked to a disorder called Huppke-Brendel syndrome, which is characterized by congenital cataracts, hearing loss, severe developmental delay and early death. It has been described in eight patients so far, who all had the abovementioned symptoms together with low serum copper and ceruloplasmin concentrations. The link between AT-1 and low ceruloplasmin concentrations is not clear, nor is the complex pathogenesis of the disease. Here we describe a further case of Huppke-Brendel syndrome with a novel and truncating homozygous gene variant and provide novel biochemical data on N-acetylated amino acids in cerebrospinal fluid (CSF) and plasma. Our results indicate that decreased levels of many N-acetylated amino acids in CSF are a typical metabolic fingerprint for AT-1 deficiency and are potential biomarkers for the defect. As acetyl-CoA is an important substrate for protein acetylation, we performed N-terminal proteomics, but found only minor effects on this particular protein modification. The acetyl-CoA content in patient's fibroblasts was insignificantly decreased. Our data may help to better understand the mechanisms underlying the metabolic disturbances, the pathophysiology and the clinical phenotype of the disease.

Lower serum copper concentrations are associated with higher prevalence of nonalcoholic steatohepatitis: a matched case–control study

Copper is an essential trace element involved in oxidative stress reactions and energy metabolism. While nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic dysfunction, the role of copper in the development of simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) is still unclear. We aimed to compare serum copper levels between patients with simple steatosis and those with NASH. We studied 102 patients with biopsy-proven NASH (cases) and 102 NAFL controls, who were matched for age, sex, and residential city. Multivariable conditional logistic analysis was performed to explore associations between serum copper levels and the presence of NASH. Serum copper levels were significantly lower in patients with NASH than in those with matched NAFL controls (15.53 ± 2.41 μmol/l vs. 16.34 ± 3.23 μmol/l; P = 0.029). This intergroup difference in serum copper levels was more pronounced in men than in women. The per unit, per SD, and per doubling of serum copper levels were associated, respectively, with an approximately 20, 40, and 90% decrease in risk of having NASH, even after adjustment for potential confounding factors. Lower serum copper concentrations are significantly associated with higher prevalence of NASH among biopsied-proven NAFLD patients, particularly in men.

Association between serum zinc and copper concentrations and copper/zinc ratio with the prevalence of knee chondrocalcinosis: a cross-sectional study

BackgroundPatients with chondrocalcinosis may suffer from a series of symptoms resembling acute gouty arthritis or septic arthritis, but the aetiology and pathogenesis of chondrocalcinosis have not been fully elucidated yet. This study was aimed to assess serum zinc and copper concentrations, as well as the ratio of serum copper to zinc concentrations (Cu/Zn ratio), in relation to the prevalence of knee chondrocalcinosis.MethodsData included in this analysis were retrieved from a large population-based cross-sectional study. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was diagnosed if definite linear cartilage calcification was detected. Serum zinc and copper concentrations were measured using the spectrophotometric flow injection methods by Roche modular P800. The relations of serum zinc and copper concentrations and Cu/Zn ratio to the prevalence of knee chondrocalcinosis were examined using generalized estimating equations, respectively.ResultsThe prevalence of knee chondrocalcinosis was 1.2% in the sample of this study (n = 12,362). In comparison with the lowest tertile, the odds ratios (ORs) of knee chondrocalcinosis adjusted by age, sex and body mass index were 0.74 (95% CI 0.50–1.09) in the second and 0.56 (95% CI 0.36–0.86) in the third tertiles of serum zinc concentrations (P for trend = 0.009), were 1.26 (95% CI 0.77–2.05) in the second and 2.01 (95% CI 1.25–3.24) in the third tertile of serum copper concentrations (P for trend = 0.003), and were 1.02 (95% CI 0.61–1.69) in the second and 2.23 (95% CI 1.38–3.59) in the third tertile of Cu/Zn ratio (P for trend < 0.001) respectively. These findings were not materially altered by adjustment for potential confounders.ConclusionsThe present study observed that higher serum zinc concentrations, lower serum copper concentrations or lower Cu/Zn ratio are associated with a lower prevalence of knee chondrocalcinosis in a dose-response relationship manner.

Estimation of Serum Copper Concentrations in Sheep and Goats Infected with Gastrointestinal Parasites in Mosul City, Iraq

The objective of the present study was to determine serum copper concentrations in sheep and goats infected with different gastrointestinal parasites. A total of 60 sheep and 30 goats were obtained from different areas in Mosul city and examined in the Veterinary Teaching Hospital, University of Mosul. Fecal and blood samples were collected from each animal. Animals infected with gastrointestinal parasites were diagnosed by detecting parasite eggs in fecal samples. Copper concentrations and hematological values were compared between infected and non-infected animals. Different gastrointestinal parasites were diagnosed include; Chabertia ovina, Cooperia spp., Haemonchus contortus, Marshallagia marshalli, Nematodirus spp., Oesophagostomum spp., Ostertagia ostertagia, Strongylus spp. and Trichostrongylus spp. in both single and mixed infection types. Infected sheep and goats suffered from different clinical signs such as emaciation, poor wool or hair, trembling, pale mucous membrane, loss of appetite, and diarrhea. Infected animals showed significantly (p≤0.05) lower serum copper concentrations compared to non-infected animals. Moreover, hematological parameters (RBC, Hb, PCV, MCH, MCV, and MCHC) were lower compared to non-infected animals. In conclusion, gastrointestinal parasitic infection in sheep and goats can decrease serum copper concentrations and blood parameters in infected animals, thereby exacerbating clinical signs.

Serum and dietary zinc and copper in Iranian girls

ObjectiveGirls with micronutrient deficiencies may have impaired growth and development, and furthermore this may also impact on their childbearing. We have investigated the relationship between serum zinc and copper concentrations, dietary zinc and copper intake and anthropometric and demographic parameters, and cardiovascular risk factors, in 408 girls living in northeastern Iran. MethodsA total of 408 healthy girls, aged 12–18 years old, were included in our study. Serum zinc and copper concentrations were measured by flame atomic absorption (Varian AA240FS) and zinc and copper intake were assessed using a 3-day dietary record. ResultsThere was a weak correlation between serum and dietary zinc intake (r = 0.117, p = 0.018). The correlation between serum and dietary copper approached significance (r = −0.094, p = 0.056). The mean serum zinc and copper concentrations were 14.61 ± 2.71 μmol/L and 19.48 ± 8.01 μmol/L respectively. Height, total cholesterol (TC) and low-density lipoprotein (LDL) were positively correlated with serum copper concentration. Subjects with high serum copper concentrations (>24 μmol/L) were found to have a significantly higher fasting blood glucose (FBG) compared to subjects with normal, or low serum copper concentrations (p = 0.033). Girls who were in the 5th percentile or greater for height were found to have higher serum copper concentrations than girls in other height categories. ConclusionThere was a weak relationship between dietary and serum concentrations of zinc. Copper status was associated with anthropometric and biochemical parameters, including FBG and lipid profile. Further studies are required to define the role of copper in metabolic health.

Serum zinc and copper concentrations and socioeconomic status in a large Persian cohort

Background: We have previously reported that serum zinc (Zn) and copper (Cu) are affected by a number of factors. In the current investigation we have investigated the association between serum Zn and Cu concentrations and socio-economic factors in an Iranian population. Materials and methods: A Persian sample population (n = 2233; n = 1106 (49.5%) males and n = 1127 (50.5%) females) was recruited by cluster-stratified sampling. Individuals were aged 15-65 years, and included urban and rural residents of the Great Khorasan province, Iran. Anthropometric measurements, serum Zn and Cu analysis and socio-economic status were determined using standard protocols. Results: The mean serum Cu and Zn concentrations for the whole group were 14.7±3.3 μmol /L (range 4.5-28.4 μmol /L), and 11.7±1.9 μmol/L (range 3.6-28.3 μmol/L) respectively, and the mean serum Zn:Cu ratio for the group was 0.83±0.2. The highest mean copper concentrations were found in the age range 50-59 years (p < 0.01). The total population of urban residents had higher serum zinc (p <0.01) and lower serum copper concentrations (p <0.05) than rural residents. Poorly educated male subjects had significantly higher serum concentrations of copper than males in the other subgroups (p <0.001). Serum Cu and Zn:Cu ratio were associated with height and body mass indices (p <0.01). Conclusion: Low serum zinc and copper appears to be common in Persian individuals. Urbanization and also educational attainment may contribute to changes in serum levels of Cu and Zn. This is probably related to lifestyle habits.

Serum Copper and Neutropenia in Elite Sailors

PURPOSE: Haematological and biochemical monitoring of an Olympic Sailing Squad was undertaken through the Beijing Olympic cycle. One aspect of this was the investigation of serum copper deficiency as a cause of neutropenia in sailors. To the authors' knowledge, this relationship has not been investigated in elite athletes. Neutrophil function has been shown to be impaired in sedentary subjects with marginal and severe copper deficiency (Bonham et al 2002). METHODS: Seventeen males and 11 females comprising the Great Britain Olympic Sailing Team. Blood samples were collected between May 2007 and November 2008; between three and on a maximum of ten occasions as part of haematological and biochemical profiling. Sampling frequency was determined by sailor availability in the U.K., and health concerns and performance. Sailors were sub-divided into a neutropenic (N) group (neutrophil count of ≤1.5) and a non-neutropenic (NN) group (neutrophil counts always ≥1.7). Samples were drawn, fasted, between 8-10 am, and 36-48 hours post training. Blood was collected for haematological analysis in K3 EDTA tubes. Serum copper was drawn into specialised trace element K2EDTA tubes. Routine and serum copper analyses were undertaken at a clinical laboratory. Serum copper (μmol/L) reflects copper status (Harvey et al 2009). Data are represented as mean (SD). The mean copper value between the N and NN groups was compared using an unequal variance unpaired t-test. RESULTS: Over 17 months a total of 28 sailors were sampled, comprising 168 blood samples. This period included the lead into Beijing Olympic Games, and post Games, and the entire Olympic Sailing Squad. The neutrophil count for the whole squad was 2.9± 0.8×103/mm3:- N 1.8 ±0.4×103/mm3; NN 3.2 ±0.6×103/mm3. Serum copper concentration for the entire squad ranged from 10.5 to 22.1μmol/L, with a mean concentration of 15.1 ±1.9 μmol/L. Serum copper for the N and NN groups, was 13.8 ±1.2 μmol/L and 15.4 ±2.0 μmol/L respectively. There was a significant difference in serum copper concentration between the N and NN groups (p<0.05). CONCLUSIONS: Sailors prone to neutropenia had lower serum copper concentrations than the non-neutropenic sailors. Low serum copper may be a cause of impaired immune function in elite athletes.

Copper Availability Contributes to Iron Perturbations in Human Nonalcoholic Fatty Liver Disease

Iron perturbations are frequently observed in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate a potential association of copper status with disturbances of iron homeostasis in NAFLD. We retrospectively studied 140 NAFLD patients and 25 control subjects. Biochemical and hepatic iron and copper parameters were analyzed. Hepatic expression of iron regulatory molecules was investigated in liver biopsy specimens by reverse-transcription polymerase chain reaction and Western blot analysis. NAFLD patients had lower hepatic copper concentrations than control subjects (21.9 +/- 9.8 vs 29.6 +/- 5.1 microg/g; P = .002). NAFLD patients with low serum and liver copper concentrations presented with higher serum ferritin levels (606.7 +/- 265.8 vs 224.2 +/- 176.0 mg/L; P < .001), increased prevalence of siderosis in liver biopsy specimens (36/46 vs 10/47 patients; P < .001), and with elevated hepatic iron concentrations (1184.4 +/- 842.7 vs 319.9 +/- 451.3 microg/g; P = .020). Lower serum concentrations of the copper-dependent ferroxidase ceruloplasmin (21.7 +/- 4.1 vs 30.4 +/- 6.4 mg/dL; P < .001) and decreased liver ferroportin (FP-1; P = .009) messenger RNA expression were found in these patients compared with NAFLD patients with high liver or serum copper concentrations. Accordingly, in rats, a reduced dietary copper intake was paralleled by a decreased hepatic FP-1 protein expression. A significant proportion of NAFLD patients should be considered copper deficient. Our results indicate that copper status is linked to iron homeostasis in NAFLD, suggesting that low copper bioavailability causes increased hepatic iron stores via decreased FP-1 expression and ceruloplasmin ferroxidase activity thus blocking liver iron export in copper-deficient subjects.

Acquisition of Visuomotor Abilities and Intellectual Quotient in Children Aged 4–10 Years: Relationship with Micronutrient Nutritional Status

Lethargy, poor attention, and the high rate and severity of infections in malnourished children affect their educational achievement. We therefore studied the association between visuomotor abilities and intelligence quotient (IQ) and their relationship with iron, zinc, and copper. A cross-sectional study was carried out on a sample of 89 healthy children (age range, 4-10 years). Evaluations of visuomotor ability and IQ were performed with the Developmental Test of Visual Motor Integration (VMI) and the Scale for Measurement of Intelligence for children aged 3-18 years, respectively. Nutritional status was assessed using anthropometry and biochemical assessments, which included serum ferritin, zinc and copper levels, and Hb. The sample was classified as having low or normal VMI scores: 47 children (52.8%, mean age 7 +/- 1.5 years) had low VMI, and 42 (47.2%, mean age 7 +/- 2.06 years) had normal VMI. There were no statistically significant differences in socioeconomic and cultural condition between both groups. We found significantly higher serum copper and ferritin levels in normal as compared to low VMI, but we did not find any differences with zinc. IQ was significantly higher in normal vs low VMI children. The fact that children with abnormal VMI presented low mean serum copper and ferritin concentrations could indicate that copper and iron deficiencies in this sample could be related with visuomotor abilities.

Genetic variation in serum copper concentration in Angus cattle

AbstractFollowing the discovery of low serum copper (Cu) concentrations in 9-month-old beef calves at pasture in autumn (50% of animals had values &lt;7·5 μmol/l), genetic variation in serum Cu concentration was studied in an experimental Angus herd in New Zealand, monitoring at intervals from about 7 to 17 months of age. The study was initiated in autumn when animals were supplemented with zinc (Zn) salts (to protect against liver injury from toxin-producing facial eczema spores on the pasture), and later in the production year after Cu supplementation but without Zn supplementation. Heritabilities of Cu concentration were estimated in 837 calves from six calf crops, the progeny of 47 sires, using restricted maximum likelihood procedures with an animal model. Correlations between Cu concentration and Zn concentration were also estimated, along with correlations between Cu concentration and 6-month, 9-month and yearling live weights. The heritability estimate for Cu concentration at all times outside the autumn Zn supplementation period was 0·28±0·08 (between-animal repeatability, 0·30±0·05), and the heritability estimates for autumn Cu concentration and Zn concentration were 0·35±0·11 and 0·26±0·13, respectively. The genetic and environmental correlations between autumn Cu concentration and Zn concentration were ?0·29±0·31 and 0·15±0·11, respectively, suggesting antagonistic effects between Zn and Cu only at the genetic level, with a net (phenotypic) correlation of 0·02±0·06. Genetic correlations between Cu concentration (outside the autumn season) and 6-month, 9-month and yearling weights ranged from 0·15±0·15 to 0·17±0·16. It was concluded that serum Cu and Zn concentrations in calves were heritable traits under the grazing conditions encountered, and that index selection to increase live weights and Cu concentrations could be applied if desired.

Relationship between Serum Copper, Ceruloplasmin, and Non–Ceruloplasmin-Bound Copper in Routine Clinical Practice

Copper is an essential cofactor for many enzymes, including cytochromes, but it is toxic in its unbound form. The vast majority of serum copper is transported bound to ceruloplasmin; the rest is bound to albumin, transcuprein, and copper–amino acid complexes. Wilson disease, an autosomal recessive disorder with a frequency of 1 in 30 000 to 1 in 100 000 live births, is caused by mutations in a P-type ATPase that prevent the incorporation of copper into ceruloplasmin (1)(2). Copper deposition occurs in hepatic parenchymal cells, the brain, the periphery of the iris, and the kidney. The age of onset and form of presentation of Wilson disease are very variable. Initially, copper accumulates in the liver, and accordingly, hepatic presentations are common (1)(2). Diagnosis of Wilson disease is a challenge (3), particularly in the absence of obvious neurologic changes, Kayser–Fleisher rings, and ophthalmic slit lamp eye examination. Low serum copper and low serum ceruloplasmin concentrations are usually seen, but some patients have concentrations within the reference intervals (2)(3)(4). Serum copper is influenced by age, acute-phase reactions, pregnancy, many anemias, and medication (oral contraceptives and antiepileptics) (5). Furthermore, ∼2% of the population who are heterozygous for P-type ATPase …

Acquired copper deficiency following prolonged jejunostomy feeds

A 19-year-old man who developed extensive oesophageal lye (Alkali) stricture and received long-term enteral nutrition (eight months) with a jejunostomy tube developed macrocytic anaemia (Hb: 41 g/L) with leucopenia (white blood cell [WBC]: 3.0 x 10(9)/L). The patient's serum vitamin B12, folate, iron and liver function tests were normal. Bone marrow examination revealed gross erythroid hyperplasia and cytoplasmic vacuolization of erythroid and myeloid elements. Further investigations revealed low serum copper (0.3 micromol/L) and ceruloplasmin concentrations (<30 mg/L) with marginally low normal serum concentration of red cell peroxidase (13 U/gHb), establishing the diagnosis of copper deficiency anaemia. The anaemia and leucopenia responded intermittently to intravenous copper therapy, but the serum copper concentration dropped when intravenous copper therapy was withdrawn. Enteral jejunostomy copper supplementation failed to maintain adequate serum copper concentrations. After stabilizing the general condition of the patient, a pharyngo-gastric anastamosis was performed and normal oral diet commenced, which restored normal serum copper concentration. This case report suggests that copper supplements in the form of copper sulphate are not adequately absorbed when administered through a jejunostomy tube.

Zincémie, cuprémie et infection chez l'enfant malnutri

Background. - Serum copper and zinc levels are decreased in malnourished and infected children. The role of either malnutrition or infection remains undetermined. Population and methods. - Serum zinc and copper concentrations were measured by atomic absorption spectrophotometry in 31 malnourished infants aged 1 to 26 months and 28 eutrophic infants aged 3 to 22 months. Fourteen infants of the first group and 10 of the second were infected at the time of study. Results. - Serum zinc and copper levels were significantly decreased in infants with malnutrition (zinc: 66 ± 32 μg/dl and copper: 81 ± 51 μg/dl versus 108 ± 26 and 185 ± 21, respectively, in eutrophic infants) (p < 0.001). These levels were still lower in those malnourished infants who were infected (zinc: 49.5 ± 18 μg/dl and copper: 63.5 ± 37 μg/dl versus 81.56 ± 35 and 94 ± 56 in non infected patients) (p < 0.02). Conclusions. - Infection increases the risk of low serum zinc and copper concentrations seen in malnourished children. This factor must be taken in account when treating malnutrition.

Osteochondrosis associated with copper deficiency in young farmed red deer and wapiti x red deer hybrids

Osteochondrosis is reported in association with copper deficiency in young red deer and wapiti X red deer hybrids on eight deer farms throughout New Zealand. On two farms, more than 30% of fawns were affected. Affected animals were lame, often had one or more swollen joints, and in some cases had an abnormal "bunny-hopping" gait or "cow-hocked" stance. Lesions were most common in the carpal, tarsal, stifle and hip joints, and were usually bilateral. Defects in articular cartilage ranged from loose flaps to complete separation with exposure of subchondral bone and the presence of cartilage fragments within the joint space. In advanced cases, the joints had features of degenerative arthropathy. Bilateral epiphyseolysis of the femoral head was observed in some severely lame deer. All deer with osteochondrosis had low serum and/or liver copper concentrations.

Skelettveränderungen bei Frühgeborenen mit Kupfermangel

We describe 5 preterm infants (25th to 30th week of gestation) suffering from alimentary copper deficiency. The diagnosis was confirmed by low serum copper and caeruloplasmin concentrations. Characteristic clinical findings were repeated apnoeic attacks, hypopigmentation of skin and hair, anaemia, neutropenia and leucopenia refractory to other therapy, as well as increasing serum alkaline phosphatase activity in the first month of life. Starting in the 3rd to 12th week of life the radiographic findings were general skeletal osteoporosis and retardation, metaphyseal radiodense lines, irregular metaphyses, cupping and spurring of the metaphyses, followed by multiple fractures and subperiosteal new bone formation and enlarged costochondral junctions. Copper was substituted orally resulting in complete healing of fractures and improvement in both clinical symptoms and laboratory parameters.

Hepatic Copper Metabolism in a Mouse Model for Menkes' Kinky Hair Syndrome

Menkes' kinky hair syndrome (KHS) is a lethal x-linked neurodegenerative disorder of copper metabolism, with low serum copper concentrations, tissue-specific copper sequestration, and decreased activities of cuproenzymes in a number of cell types. Although liver copper accumulation is abnormal in KHS, the actual defect in hepatic copper metabolism has not been elucidated. Our studies of liver copper metabolism were conducted in the mottled (blotchy) mouse, an animal model of KHS. After implantation of central venous and biliary catheters in both blotchy and control mice, we measured biliary copper excretion, hepatic copper uptake, and tissue copper contents over an 8-h period after i.v. bolus administration of radioactive 64Cu. Under the experimental conditions used, bile flow and biliary bile acid excretion were held constant, and control and blotchy hepatic 64Cu concentrations were similar in the face of the expected differential in control and mutant kidney 64Cu contents. Biliary excretion of radiocopper was 24.7 +/- 1.5% of injected 64Cu over 8 h in control animals, whereas heterozygotes excreted 6.5 +/- 1.3% and a single hemizygote excreted less than 2%. The pattern of biliary copper excretion was different, with sharp increase and steady decline in control biliary 64Cu excretion but consistently low excretion in mutant mice. No differences were observed in control or mutant hepatic uptake of 64Cu. These data show a reduced biliary excretion of copper in the blotchy mouse, in the absence of a defect in hepatic copper uptake. We suggest that defective copper transport from hepatocyte to bile represents the hepatic expression of the mottled mutation and speculate that a similar defect occurs in human KHS.(ABSTRACT TRUNCATED AT 250 WORDS)

Copper deficiency in ruminants in the South East of South Australia

Pasture development in the South East of South Australia has depended upon trace element enriched fertiliser applications. Despite the wide usage of copper-enriched fertilisers, copper deficiency is still evident in livestock at pasture, particularly cattle. Serum collected from cows and heifers during the systematic sampling program of the Brucellosis and Tuberculosis Eradication Scheme was analysed for copper. Of the 3611 pooled herd samples analysed, approximately 9% had low serum copper concentrations (&lt;7 �mol/L). Distribution of those herds identified to be at risk of copper deficiency appeared to be random, apart from areas of high risk on peat soils and the coastal fringe of calcareous sands. Analysis of pasture samples collected from paddocks with cattle having low serum copper concentrations showed that low serum copper was usually associated with raised molybdenum rather than low copper concentrations in pasture. In some instances, moderate concentrations of molybdenum and sulfur in pasture and soil ingestion associated with high iron concentrations may combine to cause hypocupraemia, especially when livestock graze stubbles and subterranean clover pastures in summer-autumn and short pastures in winter. Only 6% of pasture samples had less than 4 mg Cu/kg DM, a concentration which indicates possible copper deficiency in subterranean clover or strawberry clover.