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)

Connective tissue disorders affecting skin can be inherited or acquired and might result from an alteration of structure, function or metabolism of the constitutive elements of the supporting matrix. Collagen, the protein building the fibrous framework of the dermis, is considered as an example in understanding such a pathology at the molecular level. The molecular structure, the polymerizing capacity and the degradation of this large protein depends upon the activity of several specific post-transcriptional enzymes operating inside or outside of the cells. Pathology is known to be associated with an altered activity of most of these enzymes. Several pathological skin conditions are defined at the level of their molecular defect as in several types of the Ehlers-Danlos syndrome, osteogenesis imperfecta. Menkes' kinky hair disease, epidermolysis bullosa and scurvy. A similar molecular pathogenesis can be logically hypothesized for various other processes involving connective tissue as in scleroderma, pretibial myxoedema, cheloids, Werner syndrome, aging and corticosteroid induced atrophy.
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PMID:[Connective tissue diseases with cutaneous manifestation (author's transl)]. 75 6

Many metabolic diseases result in pathological changes within the cardiovascular system, often with the most severe effects on the function of the heart and great vessels. Metabolic disorders affecting the heart include disorders of amino acid metabolism, storage diseases, neuromuscular diseases, diseases of metal and pigment metabolism, carnitine deficiency, and connective tissue disorders. Several inborn errors of metabolism may involve the myocardium due to the accumulation of abnormal metabolites in the myocardial cells. In addition, the heart valves and coronary vessels may be involved. If the predominant effect is in the myocardial cell, it will be manifested clinically as a cardiomyopathy. Some disorders, in particular oxalosis, may involve the conduction system as a result of the deposition of oxalate crystals and result in conduction disturbances such as in alkaptonuria, primary oxalosis, and homocystinuria. Myocardial involvement may result in cardiomyopathy of the three functional types: (1) congestive, as in Fabry's disease, (2) hypertrophic, as in glycogen storage disease, type II, or (3) restrictive, as in Gaucher's disease. In the storage disease severe valvular as well as myocardial involvement occur predominantly in the glycogen storage diseases, types II-IV, mucolipidoses, sphingolipidoses, and neuronal ceroid lipofuscinosis. There are a variety of neuromuscular disorders that may be associated with cardiomyopathy, including the muscular dystrophies, Friedreich's ataxia, and Kugelberg-Welander syndrome. The pathological features of these conditions are not specific, but result usually in a congestive form of cardiomyopathy. Patients with metal and pigment metabolic disorders include iron storage disease, either hemochromatosis or transfusional hemosiderosis, Menkes' kinky hair syndrome, and Dubin-Johnson syndrome. Either a restrictive or a congestive form of cardiomyopathy may occur. The systemic form of carnitine deficiency is an autosomal recessive disorder and may present as a cardiomyopathy with congestive heart failure and lipid accumulation in the myocardial cells. Connective tissue disorders are generalized diseases that may involve the heart and valvular tissue, but also the blood vessels. These include Marfan's syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and pseudo-xanthoma elasticum.
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PMID:The effects of metabolic diseases on the cardiovascular system. 333 40

Occipital horn syndrome (OHS), an X-linked connective tissue disorder, has recently been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transporting ATPase. By Southern analysis we detected a small deletion in a region 5' to the MNK gene in one patient with OHS. Genomic clones from an unaffected individual were isolated and sequenced, revealing three tandem 98 bp repeats situated upstream of the reported transcription start site, and analysis of the patient's DNA showed a deletion of one of the repeats. The deletion is likely to be responsible for the disease in this patient, as it was not observed in 110 unaffected individuals analyzed, and no other mutation in the patient was detected by RT-PCR and chemical cleavage mismatch analysis or by cDNA sequence analysis. The deletion is associated with a dramatic decrease in expression of a chloramphenicol acetyltransferase reporter gene, implicating the repeat sequences in regulation of MNK expression, although a quantitative analysis of MNK mRNA from a cell line derived from the patient shows no detectable reduction. Other experiments revealed no effect on the site of transcription initiation, termination or on splicing.
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PMID:A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome. 892 1

Menkes syndrome is an X-linked genetic copper deficiency that is usually fatal in early childhood. Milder variants exist, including occipital horn syndrome, which is primarily a connective tissue disorder. Mutations of the mottled locus in mice produce a wide range of copper-deficient phenotypes that are good models for human diseases. Understanding the nature of the defects has been greatly increased as a result of the identification of the gene affected in Menkes syndrome. The gene spans approximately 140 kilobases, contains 23 exons, and encodes a copper-transporting ATPase termed MNK that is thought to be involved in copper efflux from cells. More recent studies show that MNK is located primarily in the trans-Golgi compartment of Chinese hamster ovary cells. Copper-resistant cells overexpress MNK and can efflux more copper than parental cells, consistent with the copper efflux role proposed for MNK. Patients with Menkes syndrome are predicted to have little or no MNK activity, whereas patients with occipital horn syndrome have less severe mutations and some residual MNK activity is predicted. Similarly, the mottled mice mutants have a range of mutations in the MNK gene homologue. Complete loss of MNK, however, produces a fetal lethal phenotype in mice. A model is proposed to explain the wide range of phenotypes exhibited by the different mouse mutants. Further research into the cell biology of copper transport is expected to reveal more about the molecular basis of copper homeostasis.
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PMID:Menkes syndrome and animal models. 958 46

A male neonate presented with an acute onset of severe intra-abdominal bleeding, haemorrhagic shock and multiple fractures leading to death on d 27. Menkes' disease was diagnosed at autopsy and confirmed by copper accumulation studies on cultured fibroblasts. Such an early onset of fatal complications in this condition has not been previously reported. New insights into the pathogenesis of Menkes' disease provided by DNA mutation analysis and difficulties in neonatal diagnosis are discussed. Menkes' disease should be considered in male infants with pathological fractures and other signs of connective tissue disease, even in the neonatal period.
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PMID:Lethal neonatal Menkes' disease with severe vasculopathy and fractures. 989 33