Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal and human studies have shown that copper is involved in the function of several enzymes. Studies have also shown that copper is required for infant growth, host defense mechanisms, bone strength, red and white cell maturation, iron transport, cholesterol and glucose metabolism, myocardial contractility, and brain development. Copper deficiency can result in the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly a pathology of infants; however, it has been diagnosed also in children and adults. Most cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia, neutropenia, and bone abnormalities. Other, less frequent manifestations are hypopigmentation of the hair, hypotonia, impaired growth, increased incidence of infections, alterations of phagocytic capacity of the neutrophils, abnormalities of cholesterol and glucose metabolism, and cardiovascular alterations. Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however, they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency.
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PMID:Copper as an essential nutrient. 861 66

A series of reports in the 1960s highlighted nutritional copper deficiencies in infants and children recovering from malnutrition in Peru; since that time, a cascade of additional cases in premature infants, in patients receiving total parenteral nutrition, and in those receiving special diets or unmodified cow milk have been reported. The identification by Danks that Menkes syndrome, a genetically determined defect in copper absorption and utilization, is responsible for the observed clinical manifestations provided further insight into the physiopathologic effects of copper deficiency. New information on the metabolism and physiologic role of copper, plus the identification of additional copper metalloenzymes and improvement in how to determine copper status, has fueled interpretation and speculation on how and why the classic signs of copper deficiency occur, as well as on the possible effects of mild deficiencies. Also under scrutiny are potential interactions between other elements and the effects of other elements, even when given in acceptable amounts, on copper status. There should be no constraints in thinking on other possible effects of impaired copper status in humans. I review some of the history of nutritional copper deficiency in infants and children and attempt to interpret some of the clinical manifestations in light of newly acquired information.
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PMID:Clinical manifestations of nutritional copper deficiency in infants and children. 958 44

Copper is an essential transition metal ion for the function of key metabolic enzymes, but its uncontrolled redox reactivity is source of reactive oxygen species. Therefore a network of transporters strictly controls the trafficking of copper in living systems. Deficit, excess, or aberrant coordination of copper are conditions that may be detrimental, especially for neuronal cells, which are particularly sensitive to oxidative stress. Indeed, the genetic disturbances of copper homeostasis, Menkes' and Wilson's diseases, are associated with neurodegeneration. Furthermore, copper interacts with the proteins that are the hallmarks of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and familial amyotrophic lateral sclerosis. In all cases, copper-mediated oxidative stress is linked to mitochondrial dysfunction, which is a common feature of neurodegeneration. In particular we recently demonstrated that in copper deficiency, mitochondrial function is impaired due to decreased activity of cytochrome c oxidase, leading to production of reactive oxygen species, which in turn triggers mitochondria-mediated apoptotic neurodegeneration.
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PMID:Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance. 1503 97

Dietary deficiency of copper results in a progressive ataxic myelopathy in ruminants called swayback. Menkes disease is a human disease due to an inherited defect in copper absorption; survival into adulthood is typically not known to occur. We report a 63-year-old woman who was evaluated by us for a myeloneuropathy that occurred in the setting of copper malabsorption. Her neurological deterioration stopped with copper supplementation. The limited literature on neurological manifestations of acquired copper deficiency suggests that the clinical presentation resembles the myeloneuropathy seen with vitamin B12 deficiency.
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PMID:Myeloneuropathy and anemia due to copper malabsorption. 1531 53

An eight month old male infant with protein energy malnutrition was admitted in the hospital with the history of repeated attacks of convulsion since four months of age. He was also suffering from frequent attacks of cough and cold since 6 months of age which was marked prior to admission. The infant had fair complexion, sparse fuzzy wooly hair with marked trunkal hypotonia. He had also mental retardation. Serum copper and ceruloplasmin levels were low, MRI showed prominent extraaxial spaces with gliosis, MR angiography revealed tortuosity of cerebral vessels. Microscopic examination of hair revealed pili torti. The patient was diagnosed as Menkes disease and treated symptomatically. For lack of facilities we were not able to do genetic study.
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PMID:Menkes kinky hair disease: A case report. 1880 Nov 84

Hair colour is one of the most conspicuous phenotypes in humans, ranging from black, brown, blond to red. This diversity arises mostly from the quantity and ratio of the black-dark brown eumelanin and the reddish-brown pheomelanin. To study the chemical basis underlying the diversity of hair colour, we have developed several chemical methods to quantify those two pigments. Alkaline H(2) O(2) oxidation affords pyrrole-2,3,5-tricarboxylic acid (PTCA) as a eumelanin marker and thiazole-2,4,5-tricarboxylic acid (TTCA) as a pheomelanin marker. Pheomelanin can also be analysed as 4-amino-3-hydroxyphenylalanine (4-AHP) after hydroiodic acid hydrolysis. Using those methods, we evaluated the contents of eumelanin and pheomelanin (the 'chemical' phenotype) in human hairs of black, dark brown, brown, light brown, blond and red colour (the 'visual' phenotype). Eumelanin contents decrease in that order, with a trace but constant level of pheomelanin, except for red hair which contains about equal levels of pheomelanin and eumelanin. Thus, the chemical phenotype correlates well with the visual phenotype. The genotype of melanocortin-1 receptor (MC1R), a gene regulating the red hair phenotype, is predictive of hair melanin expressed as the log value of eumelanin to pheomelanin ratio, with a dosage effect evident. Hair melanin contents were also analysed in patients with various hypopigmentary disorders including Hermansky-Pudlak syndrome, Menkes disease, proopiomelanocortin deficiency, cystinosis, malnutrition and trace metal deficiency. The chemical phenotype helped evaluate the precise effects of each disease on pigmentation. In studies of human hair, the chemical phenotype will find more and more application as an objective measure of pigmentation.
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PMID:Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin. 2207 70

Menkes disease is a rare neurodegenerative disorder caused by mutations in ATP7A gene. Deficiency in copper-dependent enzymes results in the unique kinky hair appearance, neurodegeneration, developmental delay, seizures, failure to thrive and other connective tissue or organ abnormalities. Other than biochemical tests, DNA-based diagnosis is now playing an important role. More than two hundred mutations in ATP7A gene were identified. Early copper supplementation can help improve neurological symptoms, but not non-neurological problems. Further molecular studies are needed to identify additional mutation types and to understand the mechanism of pathogenesis. This may help in discovering the possible treatment measures to cure the disease. We present a case with the clinical features and biochemical findings, abnormal brain magnetic resonance imaging as well as the effects of treatment with copper-histidine. Direct sequencing of ATP7A gene revealed a de novo point mutation which resulted in an early stop codon with truncated protein.
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PMID:A Truncating De Novo Point Mutation in a Young Infant with Severe Menkes Disease. 2577 38

Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD) or the rare autosomal disorder Wilson disease (WD), respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured the expression level of the two genes at various concentrations of iron, copper, and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and 10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency obtained by treatment with the copper chelator led to a downregulation of ATP7A in the control fibroblasts, but surprisingly not in the WD fibroblasts. In contrast, the addition of copper led to an increased expression of ATP7A, but a decreased expression of ATP7B. Thus, whereas similar regulation patterns for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6-8 weeks led to clonal selection. Cells that express the normal ATP7A allele had a selective growth advantage at high copper concentrations, whereas more surprisingly, cells that express the mutant ATP7A allele had a selective growth advantage at low copper concentrations. Thus, although the transcription of ATP7A is regulated by copper, clonal growth selection in mosaic cell cultures is affected by the level of copper. Female carriers of MD are rarely affected probably due to a skewed inactivation of the X-chromosome bearing the ATP7A mutation.
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PMID:Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures. 2758 95

This paper presents an overview of the physiological properties of copper (Cu), an essential trace element playing an important role in the human metabolism, primarily as a cofactor of many metalloenzymes. The maintenance of Cu homeostasis is required for proper functioning of the human body. However, when the disturbance of Cu homeostasis occurs, strong pathological manifestations may develop. Wilsons disease and idiopathic toxicosis are examples of severe chronic liver diseases that are the results of genetic predisposition to the hepatic accumulation of copper. Conversely, congenital Menkes disease is manifested as serious Cus nutritional deficiency. Although Cu is necessary for many life processes, it is also a powerful weapon used since the ancient times against many microorganisms. Finally, the theories of Cu antimicrobial and antiviral mechanisms of action are summarized, including contemporary and potential future utilizations in medical and non-medical fields of human life. Key words: copper metalloenzymes copper toxicity copper deficiency copper-related diseases copper applications.
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PMID:Biological role of copper as an essential trace element in the human organism. 3064 28

Biofortification through plant breeding is a cost-effective and sustainable approach towards addressing micronutrient malnutrition prevailing across the globe. Screening cultivars for micronutrient content and identification of quantitative trait loci (QTLs)/genes and markers help in the development of biofortified varieties in chickpea (Cicer arietinum L.). With the aim of identifying the genomic regions controlling seed Fe and Zn concentrations, the F2:3 population derived from a cross between MNK-1 and Annigeri 1 was genotyped using genotyping by sequencing approach and evaluated for Fe and Zn concentration. An intraspecific genetic linkage map comprising 839 single nucleotide polymorphisms (SNPs) spanning a total distance of 1,088.04 cM with an average marker density of 1.30 cM was constructed. By integrating the linkage map data with the phenotypic data of the F2:3 population, a total of 11 QTLs were detected for seed Fe concentration on CaLG03, CaLG04, and CaLG05, with phenotypic variation explained ranging from 7.2% (CaqFe3.4) to 13.4% (CaqFe4.2). For seed Zn concentration, eight QTLs were identified on CaLG04, CaLG05, and CaLG08. The QTLs individually explained phenotypic variations ranging between 5.7% (CaqZn8.1) and 13.7% (CaqZn4.3). Three QTLs for seed Fe and Zn concentrations (CaqFe4.4, CaqFe4.5, and CaqZn4.1) were colocated in the "QTL-hotspot" region on CaLG04 that harbors several drought tolerance-related QTLs. We identified genes in the QTL regions that encode iron-sulfur metabolism and zinc-dependent alcohol dehydrogenase activity on CaLG03, iron ion binding oxidoreductase on CaLG04, and zinc-induced facilitator-like protein and ZIP zinc/iron transport family protein on CaLG05. These genomic regions and the associated markers can be used in marker-assisted selection to increase seed Fe and Zn concentrations in agronomically superior chickpea varieties.
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PMID:Genome-Wide SNP Discovery and Mapping QTLs for Seed Iron and Zinc Concentrations in Chickpea (Cicer arietinum L.). 3315 75


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