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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