Menkes disease: Difference between revisions
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==Symptoms== |
==Symptoms== |
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Affected infants may be born prematurely. Symptoms appear during infancy and are largely a result of abnormal intestinal copper absorption with secondary deficiency in copper-dependent |
Affected infants may be [[born prematurely]]. Symptoms appear during infancy and are largely a result of abnormal intestinal copper absorption with secondary deficiency in copper-dependent [[mitochondrial]] enzymes. Normal or slightly slowed development may proceed for 2 to 3 months, and then there will be severe [[developmental delay]] and a loss of early developmental skills. Menkes Disease is also characterized by [[seizure]]s, [[failure to thrive]], [[subnormal body temperature]], and strikingly peculiar hair, which is kinky, colorless or steel-colored, and easily broken. There can be extensive neurodegeneration in the gray matter of the brain.<ref>{{cite journal | author=Barnes N, Tsivkovskii R, Tsivkovskaia N, Lutsenko S | title=The copper-transporting ATPases, menkes and wilson disease proteins, have distinct roles in adult and developing cerebellum | journal=J Biol Chem | year=2005 | pages=9640–5 | volume=280 | issue=10 | pmid=15634671 | doi=10.1074/jbc.M413840200}}</ref> Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones ([[osteoporosis]]) may result in fractures. |
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Urine [[homovanillic acid]]/[[vanillylmandelic acid]] ratio has been proposed as a screening tool to support earlier detection.<ref name="pmid15702409">{{cite journal |author=Matsuo M, Tasaki R, Kodama H, Hamasaki Y |title=Screening for Menkes disease using the urine HVA/VMA ratio |journal=J. Inherit. Metab. Dis. |volume=28 |issue=1 |pages=89–93 |year=2005 |pmid=15702409 |doi=10.1007/s10545-005-5083-6 |url=http://dx.doi.org/10.1007/s10545-005-5083-6}}</ref> |
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==Treatment== |
==Treatment== |
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Revision as of 14:14, 23 November 2008
| Menkes disease | |
|---|---|
| Specialty | Endocrinology  |
Menkes' disease (also called the kinky hair disease or Menkes kinky hair syndrome) is a disorder that affects copper levels in the body,[1] leading to copper deficiency.[2]
It was originally described by Menkes et al. in 1962.[3]
It is a X-linked recessive disorder, and is therefore considerably more common in males: females require two defective alleles to develop the disease.
Presentation
It is characterized by sparse and coarse hair, growth failure, and deterioration of the nervous system. Onset of Menkes syndrome typically begins during infancy. Signs and symptoms of this disorder include weak muscle tone (hypotonia), sagging facial features, seizures, mental retardation, and developmental delay. The patients have brittle hair and metaphyseal widening. In rare cases, symptoms begin later in childhood and are less severe.
Occipital horn syndrome (sometimes called X-linked cutis laxa), is a mild form of Menkes syndrome that begins in early to middle childhood. It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, and loose skin and joints.
Epidemiology
One European study reported a rate of 1 in 254,000.[4] A Japanese study reported a rate of 2.8 per million.[5]
Symptoms
Affected infants may be born prematurely. Symptoms appear during infancy and are largely a result of abnormal intestinal copper absorption with secondary deficiency in copper-dependent mitochondrial enzymes. Normal or slightly slowed development may proceed for 2 to 3 months, and then there will be severe developmental delay and a loss of early developmental skills. Menkes Disease is also characterized by seizures, failure to thrive, subnormal body temperature, and strikingly peculiar hair, which is kinky, colorless or steel-colored, and easily broken. There can be extensive neurodegeneration in the gray matter of the brain.[6] Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures.
Urine homovanillic acid/vanillylmandelic acid ratio has been proposed as a screening tool to support earlier detection.[7]
Treatment
Early treatment with subcutaneous (under the skin) or intravenous (in a vein) injections of copper supplements (in the form of acetate salts) may be of some benefit.[8]
Other treatment is symptomatic and supportive.
Genetics
Mutations in the ATP7A gene cause Menkes syndrome.[9] As the result of a mutation in the ATP7A gene, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the nervous system.
This condition is inherited in an X-linked recessive pattern.[10]
About one-third of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
References
- ^ "Menkes syndrome" at Dorland's Medical Dictionary
- ^ de Bie P, Muller P, Wijmenga C, Klomp LW (2007). "Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes". J. Med. Genet. 44 (11): 673–88. doi:10.1136/jmg.2007.052746. PMID 17717039.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH (1962). "A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration". Pediatrics. 29: 764–79. PMID 14472668.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Tønnesen T, Kleijer WJ, Horn N (1991). "Incidence of Menkes disease". Hum. Genet. 86 (4): 408–10. PMID 1999344.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Gu YH, Kodama H, Shiga K, Nakata S, Yanagawa Y, Ozawa H (2005). "A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis". J. Inherit. Metab. Dis. 28 (4): 473–8. doi:10.1007/s10545-005-0473-3. PMID 15902550.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Barnes N, Tsivkovskii R, Tsivkovskaia N, Lutsenko S (2005). "The copper-transporting ATPases, menkes and wilson disease proteins, have distinct roles in adult and developing cerebellum". J Biol Chem. 280 (10): 9640–5. doi:10.1074/jbc.M413840200. PMID 15634671.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Matsuo M, Tasaki R, Kodama H, Hamasaki Y (2005). "Screening for Menkes disease using the urine HVA/VMA ratio". J. Inherit. Metab. Dis. 28 (1): 89–93. doi:10.1007/s10545-005-5083-6. PMID 15702409.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kaler SG, Holmes CS, Goldstein DS; et al. (2008). "Neonatal diagnosis and treatment of Menkes disease". N. Engl. J. Med. 358 (6): 605–14. doi:10.1056/NEJMoa070613. PMID 18256395.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Voskoboinik I, Camakaris J (2002). "Menkes copper-translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease". J Bioenerg Biomembr. 34 (5): 363–71. doi:10.1023/A:1021250003104. PMID 12539963.
- ^ Kim BE, Smith K, Meagher CK, Petris MJ (2002). "A conditional mutation affecting localization of the Menkes disease copper ATPase. Suppression by copper supplementation". J. Biol. Chem. 277 (46): 44079–84. doi:10.1074/jbc.M208737200. PMID 12221109.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)