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)

This paper reports the results of a multielement analysis of postmortem samples of Menkes patients, of which one was untreated and two had been treated for various lengths of time with intramuscular injections of copper-EDTA. The findings have been compared with data from a Menkes fetus and from controls. The results confirm that copper accumulates in various tissues and demonstrate a further increase in copper levels as a result of the treatment with copper-EDTA. Although no clinical improvement was observed, the levels of some copper-containing enzymes normalized during the copper-therapy. Furthermore, in agreement with the identification of the copper-binding protein in the kidney as metallothionein, it was found that not only copper, but also zinc, cadmium, and mercury are trapped in this tissue. A low copper concentration in the brain was also found in a Menkes fetus, indicating that brain damage might already have occurred before birth. Speculation Until recently, Menkes' disease was considered to be due to copper deficiency. However, the symptoms are more typical of a storage disease in which copper is irreversibly trapped in some tissues, in particular in the kidneys, by metallothionein. This abnormal storage pattern gives rise to copper deficiency elsewhere in the organism, particularly in the brain where it may cause irreversible damage in the foetus. Parenteral administration of copper does not lead to clinical improvement. The only "therapy" that seems feasible at present is tracing the carriers of the disease and advising abortion when prenatal diagnosis indicates a male fetus carrying the disease.
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PMID:Trace element studies in three patients and a fetus with Menkes' disease. Effect of copper therapy. 678 98

Genetic disorders of copper metabolism, including Menkes kinky hair disease (MD), occipital horn syndrome (OHS) and Wilson's disease (WD) are reviewed with a focus on the neurological aspects. MD and OHS are X-linked recessive disorders characterized by a copper deficiency. Typical features of MD, such as neurologic disturbances, connective tissue disorders and hair abnormalities, can be explained by the abnormally low activity of copper-dependent enzymes. The current standard-of-care for treatment of MD is parenteral administration of copper-histidine. When the treatment is initiated in newborn babies, neurologic degeneration can be prevented, but delayed treatment is considerably less effective. Moreover, copper-histidine treatment does not improve connective tissue disorders. Novel treatments targeting neurologic and connective tissue disorders need to be developed. OHS is the mildest form of MD and is characterized by connective tissue abnormalities. Although formal trials have not been conducted for OHS, OHS patients are typically treated in a similar manner to MD. WD is an autosomal recessive disorder characterized by the toxic effects of chronic exposure to high levels of copper. Although the hepatic and nervous systems are typically most severely affected, initial symptoms are variable, making an early diagnosis difficult. Because early treatments are often critical, especially in patients with neurologic disorders, medical education efforts for an early diagnosis should target primary care physicians. Chelating agents and zinc are effective for the treatment of WD, but neurologic symptoms become temporarily worse just after treatment with chelating agents. Neurologic worsening in patients treated with tetrathiomolybdate has been reported to be lower than rates of neurologic worsening when treating with other chelating agents.
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PMID:Pathology, clinical features and treatments of congenital copper metabolic disorders--focus on neurologic aspects. 2111 68

Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson's disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome. Wilson's disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson's disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson's disease should be implemented in infants. Patients with Wilson's disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson's disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention.
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PMID:Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. 2183 3