Diseases Menkes

Diseases associated with impaired synthesis of collagen include scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome (many types), and Menkes disease. 

Menkes Disease Is Due to Mutations in the Gene Encoding a Copper-Binding P-Type ATPase... 

Menkes disease ( kinky or steely hair disease) is a disorder of copper metabolism. It is X-hnked, affects... 

The cause of Wilson disease was also revealed in 1993, when it was reported that a variety of mutations in a gene encoding a copper-binding P-type ATPase were responsible. The gene is estimated to encode a protein of 1411 amino acids, which is highly homologous to the product of the gene affected in Menkes disease. In a manner not yet fully explained, a nonfunctional ATPase causes defective excretion of copper into the bile, a reduction of incorporation of copper into... 

Ceruloplasmin contains substantial amounts of copper, but albumin appears to be more important with regard to its transport. Both Wilson disease and Menkes disease, which reflect abnormahties of copper metabohsm, have been found to be due to mutations in genes encoding copper-binding P-type ATPases. 

Abnormalities in copper metabolism are normally associated with Wilson s disease [28] and Menkes disease [29,30,31], although total copper and hCP concentrations increase significantly in many inflammatory and infectious diseases including hepatitis and tuberculosis, and a number of different kinds of cancer. A direct connection between copper and coronary artery disease has also been proposed [32]. A useful general review of copper and disease has been given by Linder [33]. 

Strain genetically deficient in copper (Menkes disease) given subcutaneous injections of 50 pg copper chloride (CuCI2) on postnatal days 7 and 10. Before therapy, liver copper concentration was 3.1 mg/kg FW (vs. 30.1 mg/kg FW in normal mice)... 

The amino acid histidine is used for the treatment of copper overload in Wilson s disease and forms a strong 1 2 complex (Fig. 27) (553). Copper-histidine therapy is also an efficient treatment for copper deficiency in Menkes disease (554). 

Menkes disease, an X-linked recessive condition, is caused by mutations in the gene encoding a Cu efflux protein. Cells from an affected individual accumulate high concentrations of Cu " that cannot be released from the cell. The symptoms result from functional Cu deficiency inasmuch as Cu absorbed from the intestine becomes trapped in the intestinal epithelial cells and delivery to other tissues is inadequate. 

Menkes disease Deficient cross-linking secondary to functional copper deficiency Depigmented (steely) hair Arterial tortuosity, rupture Cerebral degeneration Osteoporosis, anemia... 

Menaquinones (vitamin K2) 818, 821 Mengo virus 247 Menkes disease 883 Mercaptans 624 Mercaptides 550 Mercaptoethanol 98... 

The causes of human copper deficiency include (1) low intake - malnutrition, total parenteral nutrition (TPN) (2) high loss - cystic fibrosis, nephrotic syndromes and (3) genetic factors — Menkes disease. Copper deficiency may also be associated with chronic malabsorption, a situation which is made much worse in cases of gastric and bowel resection. Several special diets, including powdered milk, liquid protein and standard hospital diets are a means of inducing copper deficiency. The amount of copper in US food has decreased steadily since 1942, and may be related to the rising incidence of coronary artery disease. A copper deficiency may also occur as the result of the use of chelators for other purposes for example, diethyl dithiocarbamate is an in vivo metabolite of ANTABUSE (disulfiram). 

Two genetic disorders of copper metabolism, Wilson s disease (see Section 62.2.3.3) and Menkes disease, are known. The latter involves impaired intestinal absorption of copper56,57 as well as probably subcellular metabolic defects which result in copper deficiency with respect to metal-loenzyme activity. The characteristic steely hair in Menkes disease results from free SH bonds in hair protein because of failure of lysyl oxidase to produce the disulfide links. Depigmentation of hair and skin, hypothermia, cerebral degeneration, central nervous system retardation, skeletal demineralization and arterial degeneration are all seen. Copper supplements may benefit hypothermia and increase pigmentation but the disease is not generally cured. 

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