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 What is Menkes Disease?
Menkes disease is caused by a defective
gene that regulates the metabolism of copper in the body. The disease primarily affects male infants. Copper
accumulates at abnormally low levels in the liver and brain, but at higher than normal levels in the kidney
and intestinal lining. Affected infants may be born prematurely, but appear healthy at birth and develop
normally for 6 to 8 weeks. Then symptoms begin, including floppy muscle tone, seizures, and failure to
thrive. Menkes disease is also characterized by subnormal body temperature and strikingly peculiar hair,
which is kinky, colorless or steel-colored, and breaks easily. There is often extensive neurodegeneration in
the gray matter of the brain. Arteries in the brain may 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.
| More details about Menkes
Disease |
Menkes disease, also known as kinky hair disease, is an X-linked neurodegenerative
disease of impaired copper transport. Menkes et al first described it in 1962. Danks et al
first noted that copper metabolism is abnormal in 1972; in 1973, after noting the
similarity of kinky hair to the brittle wool of Australian sheep raised in areas with
copper-deficient soil, he demonstrated abnormal levels of copper and ceruloplasmin in these
patients.
A girl with the Menkes disease phenotype and an X:autosome chromosomal translocation was
described in 1987, which led to the identification of the locus on the X chromosome in
1993. Milder variants of Menkes disease, including occipital horn syndrome (also known as
X-linked cutis laxa or Ehlers-Danlos type 9) have also been described. The brindled mouse,
viable brindled mouse, and blotchy mouse are animal models of the classic form, the mild
form, and the occipital horn syndrome, respectively.
Is there any treatment?
Treatment with daily copper injections may improve the outcome in Menkes disease if it
begins within days after birth. Other treatment is symptomatic and supportive.
What is the prognosis?
Since newborn screening for this disorder is not available, and early detection is
infrequent because the clinical signs of Menkes disease are subtle in the beginning, the
disease is rarely treated early enough to make a significant difference. The prognosis for
babies with Menkes disease is poor. Most children with Menkes disease die within the first
decade of life.
What research is being
done?
Recent research sponsored by the NINDS developed a blood test that could be given to
newborns at risk for Menkes disease based on a positive family history for the disorder or
other indications. The test measures 4 different chemicals in the blood and, depending upon
their levels, can accurately diagnose the presence of Menkes disease before symptoms appear.
Study results showed higher survival rates for children given the earliest copper injection
treatment and improved, if not normal, neurodevelopment.
Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations
in a copper-transport gene, ATP7A. Early treatment with copper injections may prevent
death and illness, but presymptomatic detection is hindered by the inadequate sensitivity and
specificity of diagnostic tests. Exploiting the deficiency of a copper enzyme,
dopamine-β-hydroxylase, we prospectively evaluated the diagnostic usefulness of plasma
neurochemical levels, assessed the clinical effect of early detection, and investigated the
molecular bases for treatment outcomes.
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Menkes syndrome is an inborn error of metabolism that markedly decreases the cells' ability to absorb copper.
The disorder causes severe cerebral degeneration and arterial changes, resulting in death in infancy. The disease
can often be diagnosed by looking at a victim's hair, which appears to be both whitish and kinked when viewed under
a microscope.
Menkes' disease is transmitted as an X-linked recessive trait. Sufferers can not transport copper, which is
needed by enzymes involved in making bone, nerve and other structures. A number of other diseases, including type
IX Ehlers-Danlos syndrome, may be the result of allelic mutations (i.e. mutations in the same gene, but having
slightly different symptoms) and it is hoped that research into these diseases may prove useful in fighting Menkes'
disease.
If administered within the first few months of life, copper histidinate appears to be effective in increasing
the life expectancy of some patients. However, this treatment only increases life expectancy from three to thirteen
years of age, so can only be considered a palliative. A similar condition to Menkes' disease exists in mice;
working with these model organisms will help give insight into human copper transport mechanisms, so helping to
develop effective treatments for Menkes' sufferers.
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