Clinical utility gene card for: Menkes disease

Tümer, Zeynep; Klomp, Leo W. J.

doi:10.1038/ejhg.2011.56

Cited by 2 publications

(1 citation statement)

References 11 publications

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“…The initial diagnosis of MD is suggested by the clinical features (especially the typical hair changes) and supported by the demonstration of reduced levels of serum copper and ceruloplasmin [Tümer and Klomp, ]. However, in the neonatal period, these markers should be interpreted with caution, as their levels are low also in healthy newborns.…”

Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

An Overview and Update ofATP7AMutations Leading to Menkes Disease and Occipital Horn Syndrome

2013

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Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar "kinky" hair, are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs because of mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy-dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms. This study reviews 274 published and 18 novel disease causing mutations identified in 370 unrelated MD patients, nonpathogenic variants of ATP7A, functional studies of the ATP7A mutations, and animal models of MD.

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Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

An Overview and Update ofATP7AMutations Leading to Menkes Disease and Occipital Horn Syndrome

2013

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Copper Metabolism,ATP7AandMenkes Disease

Pierson

Lutsenko

Tümer

2015

Encyclopedia of Life Sciences

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ATP7A is an ATP‐driven copper transport protein that plays an essential role in human health. ATP7A is critically involved in dietary copper uptake in the intestine. In addition, ATP7A delivers copper to numerous copper‐dependent enzymes within the secretory pathway and facilitates copper transfer to the brain. Inactivating mutations in ATP7A are associated with severe and often lethal pathologies, such as Menkes disease, occipital horn syndrome, and distal motor neuropathy. Genetic and biochemical studies have demonstrated that disease‐causing mutations disrupt ATP7A in many ways, including disruption of biosynthesis, impairment of stability, inactivation of copper transport activity and disturbance of trafficking behaviour. Cellular studies also indicate that ATP7A is a subject of complex regulation. Despite significant progress in the characterisation of ATP7A's function, cell‐specific regulation of this transporter remains poorly understood. Many aspects of pathologies caused by mutations in ATP7A require further in depth studies. Key Concepts Copper is the third most abundant trace element in the body, after iron and zinc, and it is required for normal function of important copper‐dependent enzymes. Copper deficiency is detrimental to the development and function of many organs especially the central nervous system. Precise regulation of intracellular copper levels is vitally important because, although essential, excess copper has detrimental effects on metabolism. Several transporter molecules and carrier proteins are involved in regulating copper homeostasis. ATP7A is a member of a large family of P‐type ATPases. These ATP‐utilising membrane proteins pump ions across cellular membranes against a concentration gradient. ATP7A is involved in the delivery of copper to cuproenzymes in the secretory pathway and in the export of surplus copper from cells. Genetic defects in ATP7A leads to the X‐linked recessive Menkes disease. Menkes disease is a multi‐systemic lethal disorder, marked by neurodegenerative symptoms and connective tissue manifestations. Most of the clinical features of Menkes disease can be explained by deficiency of various copper‐dependent enzymes. ATP7A mutations vary from single nucleotide changes to microscopically detectable chromosome abnormalities. Ultimate diagnostic proof of Menkes disease is the demonstration of the molecular defect in ATP7A . Menkes disease patients show progressive deterioration of brain function. Administration of copper‐histidine before brain damage may slow the disease progression and result in less severe neurological symptoms.

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Clinical utility gene card for: Menkes disease

Cited by 2 publications

References 11 publications

An Overview and Update ofATP7AMutations Leading to Menkes Disease and Occipital Horn Syndrome

An Overview and Update ofATP7AMutations Leading to Menkes Disease and Occipital Horn Syndrome

Copper Metabolism,ATP7AandMenkes Disease

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