Menke’s syndrome

Menke s syndrome (kinky hair disease) + + +/- Males with wormian bones, low serum copper and tortuous intracranial vessels... 

Hair serves to eliminate toxic materials (e.g., lead) and metabolites from the body, and may be used to monitor environmental contamination. For example, copper deficiency is a cause of Menke s kinky hair syndrome protein deficiency leads to hair loss and discoloration. Hair keratin carries a strong negative charge and binds inorganic materials it becomes prone to... 

Copper is an essential element to most life forms. In humans it is the third most abundant trace element only iron and zinc are present in higher quantity. Utilization of copper usually involves a protein active site which catalyzes a critical oxidation reaction, e.g., cytochrome oxidase, amine oxidases, superoxide dismutase, ferroxidases, dopamine-/ -hydrox-ylase, and tyrosinase. Accordingly, animals exhibit unique homeostatic mechanisms for the absorption, distribution, utilization, and excretion of copper (J). Moreover, at least two potentially lethal inherited diseases of copper metabolism are known Wilson s Disease and Menkes s Kinky Hair Syndrome (I). 

An X-linked, inherited abnormality in mice (mottled mouse syndrome) provides an animal model for the human disease [ 19]. Results illustrate that the copper metabolism disturbance already manifests itself in utero and that the gene for Menkes s disease results in organ-specific accumulations and depletions rather than in an overall copper deficiency in the body. It has been found that the brain levels in affected fetuses are not significantly different from those of age-matched controls. But brain levels increase after birth in normal subjects whereas the levels of affected males become clearly reduced. 

Danks, D. M., Campbell, P, E., Stevens, B. J., Mayne, V., and Cartwright, E, (1972a) Menkes s kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics 50 188. 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

Copper Anaemia Menkes (kinky hair) syndrome Cardiac abnormalities/heart disease Wilson s disease Hepatic injury and jaundice Headache, vomiting Haemolytic shock... 

Important disorders associated with transition metals include insufficient intake or absorption (e.g. iron deficiency anaemia), defective transport (e.g. Menkes syndrome), and excessive storage (e.g. Wilson s disease, haemochromatosis). 

The human hereditary disorders Wilson s disease and Menkes disease have provided further insight into copper metabolism. In Wilson s disease the ceruloplasmin content is low and copper gradually accumulates to high levels in the liver and brain. In Menkes syndrome, there is also a low ceruloplasmin level and an accumulation of copper in the form of... 

Although genetic defects in the metahoUsm of trace elements are rare, they are nonetheless important because of the information they have provided as to homeostatic control mechanisms. This in turn has led to development of effective therapeutic strategies. The most commonly investigated disorders are those affecting iron (hemochromatosis), copper (Wilson s disease and Menkes syndrome), zinc (acrodermatitis enteropathica), and molybdenum (molybdenum cofactor disease). 

Copper is necessary, together with iron, for hematopoiesis, probably partly because it is needed for the synthesis of fer-roxidase (ceruloplasmin). Many enzymes require copper for activity. Examples of some of the copper-enzymes and their functions are given in Table 37-5. Mitochondrial iron uptake may be blocked by deficiency of a cuproprotein, perhaps cytochrome oxidase. Several inherited diseases involving abnormalities in copper metabolism (Wilson s disease, Menkes syndrome) or copper enzymes (X-linked cutis laxa, albinism) occur in human and in several animal species. 

The molecular defect in Menkens syndrome, like that in Wilson s disease, resides in a P-type ATPase. The gene for the enzyme is located on the X chromosome. Wilson s disease is characterized by defective biliary excretion in Menkes syndrome, the defect is a failure to transport copper to the fetus during development as well as failure to absorb copper from the gastrointestinal tract after birth. 

There are two inbttrn errors of ettpper metabolism Menkes syndrome and Wilson s disease. 

With the exception of genetically impaired individuals with Menkes disease and Wilson s disease, individuals who suffer from various grossly inadequate diets, diarrhea and severe malnutrition, and the patients who suffer from primary biliary cirrhosis, and cholestatic syndromes of Indian childhood cirrhosis, the development of copper deficiency and toxicity is not a significant risk for man. 

Ceruloplasmin (EC 1.12.3.1) Plasma 132 6 Blue Polyamine oxidase ferroxidase Unkno m Deficient or absent in Wilson s disease. and in Menkes syndrome Glycoprotein... 

Packman S, O Toole C, Price DC, Thaler MM (1983) Cadmium, zinc, and copper metabolism in the mottled mouse, an animal model for Menkes kinky hair syndrome. J Inorg Biochem 19 203-211... 

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