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)

The authors report the sixth case of Menkes' kinky hair disease. This boy has been observed for as long as 16 months, and he his still alive at the time of publication. This genetic, X linked disorder of copper metabolism is always fatal in childhood. Diagnosis is evoked when is noted the conjunction of progressive cerebral degeneration, seizures, with pili torti and monilethrix. It can be asserted with the very low copper and cerulo-plasmin blood levels. Recognition of the disease in utero might be possible. New findings in skin' electron microscopy and hair' scanning electron microscopy are reported here. And two RX scanner of the brain have been performed.
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PMID:[Menkes' disease (new skin and hair ultrastructural abnormalities) (author's transl)]. 70 42

The difficulties of early diagnosis of Menkes' kinky hair syndrome are described guided by the clinical courses of three related patients. One of these children could be observed continuously from birth. Different from other descriptions the diagnostic value of the clinical features observed in our patients is estimated as follows: 1. severe cerebral degeneration with seizures in the first year of life; 2. subdural hygroma; 3. decreased levels of serum copper and serum coeruloplasmin; 4. hair abnormalities; 5. skin abnormalities. The diagnosis is likely, if serum copper and serum coeruloplasmin are decreased. The diagnosis is proved by increased copper uptake into cultured fibroblasts. The prenatal diagnosis is possible by chorionic villus biopsy or amniocentesis. The importance of carrier detection by cultured fibroblasts and subsequent genetic counselling is underlined.
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PMID:[Clinical aspects of Menkes syndrome]. 343 7

Menkes' steely-hair disease is characterized by abnormal copper metabolism accompanying progressive cerebral degeneration. Cerebral lipids and proteins of an infantile male patient with Menkes' disease were analyzed. The major lipid components in myelin, which included free cholesterol, phospholipids, galactosylceramide, sulfatide, and GM4 ganglioside were markedly decreased, indicating that the myelin was severely damaged by the defective copper metabolism. The degeneration of the myelin was also indicated by decrease in myelin basic protein and proteolipid protein, whereas gliosis in the white matter was biochemically confirmed by prominent increase in glial fibrillary acidic protein. Fatty acid analyses of phospholipids in the white matter revealed that the unsaturated fatty acids were severely decreased in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine, and that the long chain fatty acids were also decreased in sphingomyelin. As both the desaturation of fatty acids in glycerophospholipids and the elongation of fatty acids in sphingomyelin are in general thought as markers for myelination, the results suggest that the progressive cerebral degeneration in the disease is due to dysmyelination rather than demyelination. The dysmyelination seemed to be supported by the fact that cholesterol ester which is thought as a marker for demyelination, showed no increase in the brain.
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PMID:Cerebral lipid and protein abnormalities in Menkes' steely-hair disease. 359 92

Menkes' Kinky Hair Syndrome (MKHS) comprises an array of clinical manifestations including hair shaft abnormalities, epidermal hypopigmentation, and progressive cerebral degeneration that are transmitted as an X-linked recessive disorder affecting copper transport pathways in primarily young males. The oral manifestations of MKHS are scantly reported to include the presence of gingival enlargement and delayed eruption of primary teeth. The purpose of this report is to present a case of MKHS describing the intraoral clinical findings.
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PMID:Oral manifestations of Menkes' kinky hair syndrome. 1149 14

Menkes' disease is a rare X-linked multisystemic lethal disorder of copper transport metabolism. Failure of synthesis of several copper enzymes explains most of the clinical features, which were characterised by neurodegenerative symptoms and connective tissue manifestations. Most cases are still prone to rapidly progressive cerebral degeneration and early death in the first few years. Since CNS-dysfunction usually preceeds development of the pathognomonic "steely" hair, delay of clinical diagnosis and onset of therapeutic intervention precludes longlasting neurological benefit. This is particularly true for patients with large deletions or severe truncations of the responsible ATP7A gene. We report on our own experience with a patient, who was diagnosed to be affected by Menkes' syndrome at the age of one year, due to the specific hair texture and biochemical abnormalities. Molecular investigation revealed a total deletion of exon 15 of the ATP7A gene. Heterozygosity was confirmed by means of real-time PCR in the child's mother, but could be excluded in the grandmother and other female relatives at risk. Therapeutic support with subcutaneous injection of copper-histidinate normalised diminished copper and coeruloplasmin serum levels, but was unable to influence the clinical course and to prevent the fatal outcome at the age of two years. This observation is in line with the experience of the literature claiming that currently available medication will hardly be able to normalise brain copper levels. However, observations of clinical variants of Menkes' disease with quite a different outcome and, more importantly, emerging of alternative copper transport pathways might still justify this time-limited therapeutic intervention.
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PMID:[Menkes' disease: heterozygosity testing by quantitative real-time PCR and the dilemma of therapeutic support]. 1616 77

The copper-transporting ATPase ATP7A contains eight transmembrane domains and is required for normal human copper homeostasis. Mutations in the ATP7A gene may lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn syndrome (OHS), a related but much milder illness; or an adult-onset isolated distal motor neuropathy. The ATP7A missense mutation T994I is located in the sixth transmembrane domain of ATP7A, represents one of the variants associated with the latter phenotype, and is associated with an abnormal interaction with p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated with diverse cellular activities) with multiple biological functions. In this study, we further characterized this interaction and discovered a concealed UBX domain in the third lumenal loop of ATP7A, between its fifth and sixth transmembrane domains. We show that the T994I substitution results in conformational exposure of the UBX domain, which then binds the N-terminal domain of p97/VCP. We also show that this abnormal interaction occurs at or near the cell plasma membrane. The UBX domain has a conserved hydrophobic FP (Phe-Pro) motif, and substitution with di-alanine abrogated the interaction and restored the proper intracellular localization of ATP7A in the trans-Golgi network. Using protein MS, we identified potential coordinating components of the ATP7AT994I-p97 complex, including NSFL1 cofactor (NSF1C or p47) that may be relevant to the pathophysiology and clinical effects associated with ATP7AT994I Our study represents the first report of p97/VCP binding to a UBX domain that is not normally exposed, resulting in an aberrant protein-protein interaction leading to motor neuron degeneration.
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PMID:Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration. 2959 89