Infantile Neurodegeneration and Hair Changes: A Rare Case of Menkes Disease

A 4-month-old, previously healthy boy presented with acute onset of prolonged, recurrent seizure activity followed by neurodevelopmental deterioration and concurrent hair shaft hypopigmentation with fragility. Initial evaluation revealed significant low serum copper and ceruloplasmin, electrical status epilepticus on electroencephalography, and generalized subcortical white matter changes with diffuse tortuosity of intracranial vessels on MRI brain. In addition, a genetic study with whole-genome sequencing demonstrated a hemizygous pathogenic variant at c.2179G>A p(Gly727Arg) on ATP7A, thereby confirming the diagnosis of Menkes disease. Symptomatic treatment with antiepileptic medications was provided along with an urgent referral to an advanced center for multidisciplinary care and copper histidine replacement therapy.

Administration of zinc to preterm infants with hypozincemia does not reduce serum copper concentrations in most cases: a single-center retrospective observational study

Background Zinc is an essential trace element involved in various physiological functions. In Japan, zinc acetate dihydrate is administered to neonates and infants with hypozincemia. Since serum copper concentrations are reduced by the administration of zinc, we retrospectively investigated changes in serum zinc and copper concentrations in preterm infants with hypozincemia receiving zinc acetate dihydrate. Methods Sixty-three preterm infants were included in the present study. Serum zinc and copper concentrations, doses, and other clinical characteristics were retrieved from electronic medical records. Results The medians and interquartile ranges of the dosage and duration of zinc acetate dihydrate were 2.1 (1.8–2.5) mg/kg/day and 12.0 (10.0–13.0) days, respectively. Its administration increased serum zinc concentrations in 39 patients (61.9%) and to more than 70 μg/dL in 16 patients (25.4%). The group with a serum zinc concentration of 70 μg/dL or higher after administration had a significantly higher zinc dose of 2.5 mg/kg/day than the group with a serum zinc concentration of less than 70 μg/dL. Serum copper concentrations did not decrease in 44 patients (69.8%). In the group with a decreased serum copper concentration, postmenstrual age and body weight were significantly lower, while serum zinc concentrations were significantly higher at the start of administration. Conclusion The present results showed that when zinc acetate dihydrate was administered to preterm infants with hypozincemia, it was possible to increase serum zinc concentrations without decreasing serum copper concentrations in many cases. However, caution may be required when administering zinc to preterm infants with a lower postmenstrual age or milder hypozincemia because serum copper concentrations may decrease.

Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report

Background Subacute combined degeneration (SCD) is a neurological complication commonly associated with vitamin B12 deficiency. It can result from nitrous oxide (N2O) abuse and cause neuropsychiatric symptoms. However, there has been no literature regarding alterations of serum copper and cerebellum in SCD patients. Case presentation We reported two cases of young SCD patients with histories of N2O abuse. In these cases, elevated homocysteine, macrocytic anemia, spinal cord abnormalities, and peripheral nerve injuries were detected. In addition, decreased serum copper level and cerebellar atrophy were reported for the first time. The patients’ symptoms improved after withdrawal of N2O exposure and vitamin B12 supplements. Conclusion We reported two SCD cases with serum copper alteration and cerebellar atrophy after N2O abuse for the first time. These might be crucial complements to the diagnosis of SCD.

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer

Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions.Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort).Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621–0.757; C-index for OS: 0.728, 95% CI: 0.654–0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort.Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

Circulating Serum Copper Is Associated with Atherosclerotic Cardiovascular Disease, but Not Venous Thromboembolism: A Prospective Cohort Study

<b><i>Background and Objective:</i></b> Serum copper has been linked to the risk of atherosclerotic cardiovascular disease (CVD). However, the potential association between serum copper and venous thromboembolism (VTE) is not known. The principal aim was to evaluate the potential prospective association between serum copper and VTE risk. A secondary aim was to confirm or refute previously reported associations between serum copper and atherosclerotic CVD. <b><i>Methods:</i></b> Serum copper was measured at baseline using atomic absorption spectrometry in 2,492 men aged 42–61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort study. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence interval (CI) for VTE. <b><i>Results:</i></b> During a median follow-up of 27.0 years, 166 VTE events occurred. The risk of VTE per 1 standard deviation increase in serum copper in age-adjusted analysis was HR: 1.02; 95% CI: 0.88–1.20, which was attenuated to HR: 0.99; 95% CI: 0.82–1.19, following further adjustment for several established and emerging risk factors. Comparing the top versus bottom tertiles of serum copper, the corresponding adjusted HRs were 1.16 (95% CI: 0.80–1.66) and 1.11 (95% CI: 0.74–1.68), respectively. In 1,901 men without a history of coronary heart disease (CHD), the multivariable-adjusted HR for CHD was 1.32 (95% CI: 1.10–1.59) comparing extreme tertiles of serum copper. <b><i>Conclusion:</i></b> In middle-aged Finnish men, we confirmed previously reported associations between high serum copper levels and increased risk of atherosclerotic CVD, but serum copper was not associated with future VTE risk. Other large-scale prospective studies conducted in women, other age-groups, and other populations are needed to confirm or refute these findings.

Association of Serum Copper Levels and Amine Oxidase Copper Gene 1 (AOC1) with Migraineurs

Migraine is a common neurovascular multifactorial disease with biochemical abnormalities in the central nervous system (CNS). It is characterized by episodes of frequent headaches, affecting about 14% of the world's population. Trace elements are essential to play an important role in neurotransmission and causing oxidative stress in patients with migraine. Also, it is hypothesized that Histamine (biogenic amine), catabolized by Diamine oxidase (DAO), induces a vascular headache. DAO contains Copper as a cofactor and is coded by the Amine oxidase copper containing 1 (AOC1) gene. This study aims to determine the level of serum copper (Cu), an association of the AOC1 gene and antioxidant capacity in migraine patients. In this study, a total number of 200 individuals (patients and controls) were equally distributed in each group according to demographic details obtained. The results obtained from this study were found to be significant to migraine. The frequency of T allele (rs10156191) in exon 4 AOC1 was 7.5% in migraineurs OR of 16.13; 95% CI- 0.63 to 47.97, and the p-value was observed to be 0.074. The mean concentration of Cu was found to be 0.09 ± 0.02 mg/L and 0.22 ± 0.10 mg/L in patients and controls, respectively. Antioxidant capacity of serum was found to be lower in patients (3 ± 1.2 μM ascorbic acid equivalents) when compared to controls (7 ± 0.9 μM ascorbic acid equivalents). Decreased Cu and a nonsynonymous of rs10156191 are associated with migraine, which may decrease in DAO activity. Further research, needs to be focused on the DAO activity that can determine the migraine-inducing effect.

Copper and Copper/Zn Ratio in a Series of Children with Chronic Diseases: A Cross-Sectional Study

Copper is an essential micronutrient for humans. A cross-sectional and comparative study was done to assess serum Cu levels and serum copper/zinc (Cu/Zn) ratio and its association with nutritional indicators in a series of children and adolescents with chronic diseases. Anthropometric, biochemical, dietary, body composition, and bone densitometry assessments were carried out. Serum Cu and Zn were measured by atomic absorption spectrophotometry. Seventy-eight patients (55% women) participated. The mean serum Cu in the entire series and by nutritional status through body mass index (BMI) was normal. Serum Cu decreased significantly with age and was meaningfully higher in children than in adolescents. The risk of finding altered Cu levels in children and men was higher than in adolescents and women, respectively. Twenty-two per cent of patients had abnormal serum copper levels, 13 had hypercupremia, and four had hypocupremia. The Cu/Zn ratio was greater than 1.00 for 87% of the patients, which is an indicator of an inflammatory state. All patients with hypozincemia and hypocupremia had deficient Zn intake, but only 65% of the patients with hypercupremia had dietary Zn deficiency. Consequently, the Cu/Zn ratio could indicate an inflammatory state and a high risk of zinc deficiency in this specific child population.

Study on serum zinc and copper levels in pulmonary tuberculosis patients before starting Directly Observed Treatment, Short-course

Background: Tuberculosis is a major public health concern throughout the world including Bangladesh. The prevalence of tuberculosis (TB) is increasing day by day. Around one-third of world population is infected with M. tuberculosis. Still pulmonary tuberculosis (PTB) remains one of the important causes of mortality throughout the world with economic burden. Objective: To evaluate levels of the serum zinc and serum copper in smear positive PTB patients before starting Directly Observed Treatment, Short-course (DOTs) therapy. Methods: This was a cross-sectional type of observational study. A total of 100 subjects were included in this study. Among them 50 were smear positive PTB patients denoted as case group and 50 were apparently healthy individuals denoted as control group. Biochemical tests were carried out in the department of biochemistry of Mymensingh Medical College, Mymensingh. All the statistical analyses were performed by using SPSS version 21. Results were evaluated by using Student’s t-test. Results: After careful evaluation there was significant decrease in serum zinc level along with significant increase in serum copper level among the case group when compared with the control group. The mean values of serum zinc level were 93.96±10.04 μg/dl and 72.84±7.73 μg/dl in control and case group respectively. Serum zinc level decreased significantly (p <0.001) in PTB patients. The mean values of serum copper were 111.81±21.26 μg/dl and 125.99±27.93 μg/dl in control and case group respectively. There was significant (p <0.001) rise of serum copper level in PTB patients. Mediscope 2021;8(2): 122-127