Menkes Syndrome
by Michel Perron
Menkes syndrome has been found to be a genetically inherited disorder that
primarily affects male infants and children (Females have been identified
with Menkes syndrome due to an x-autosome translocation). The gene responsible
for this condition, Mnk, resides on the X chromosome at the Xq13.3 loci
and has the inheritance pattern of an X-linked recessive disorder. This
loci which codes for a 4.5 kb transcript produces a 1500 residue polypeptide
ATPase (designated ATP7A1-5) that is capable of copper transport through
use of an aspartyl phosphate intermediate. The mRNA in two individuals with
Menkes syndrome have been found by Tumer et al (1996) to contain a single
deletion within exon 4 and 12 leading to truncated proteins due to a frameshift
mutation. This inability of copper absorption leads to increased levels
of copper-metallothionein complexes within affected fibroblasts by a factor
of 5 over normal fibroblasts. This error in copper metabolism has profound
effects on copper dependent enzymes function as can be seen below:
enzyme condition due to decreased copper levels
lysyl oxidase defect in elastin and collagen crosslinks
leading to arterial abnormalities
ascorbic acid oxidase skeletal defects similar to scurvy due to
inadequate vitamin C production
tyrosinase depigmentation of skin and hair
cytochrome C oxidase hypothermia
enzymes that form kinky hair
disulfide bonds in keritin
Due to decreased activity of copper based enzymes several phenotypes are
common in individuals with Menkes syndrome. Most notably individuals develop
whitish hair due to pili torti, monilethrix and trichorrhexis nodosa. Gradual
cerebral and cerebellar degredation, major seizures, aberrant tortuous arteries,
skeletal abnormalities and premature death are among the most serious effects
of Menkes syndrome. There is currently no adaquate treatment for this genetic
disease although it has been discovered that copper histidinate injections,
if administered early enough, may prevent cerebral deterioration-due to
its ability to cross the blood brain barrier- and hair discoloration and
abnormalities.
In the case with Mertha and Eliot D. son, Rick, a clear distinct link exists
between the phenotypes described above and Ricks phenotypes- white hair,
brain degeneration, artery abnormalities, bending of legs bones similar
to scurvy. It is also evident that this disease was inherited from the mother
due to signs of unusual twisting of her hair and because of the X-linked
recessive inheritance pattern.
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