Total Posts: 11
|Posted: Fri Feb 01, 2008 03:46 am|
You all know the famous disease of copper metabolism, the Wilson's Disease. But do you know about Menkes (Kinky Hair) Disease, another disorder associated with Copper metabolism?
Menkes disease (kinky hair disease) is a progressive neurodegenerative condition inherited as a sex-linked recessive trait. The MNK gene is organized in 23 exons spanning approximately 150 kb. The gene has been mapped to Xq13.3.
Symptoms begin during the first few months of life and include hypothermia, hypotonia, and generalized myoclonic seizures. The facies are distinctive, with chubby, rosy cheeks and kinky, colorless, friable hair. Microscopic examination of the hair shows several abnormalities, including trichorrhexis nodosa (fractures along the hair shaft) and pili torti (twisted hair). Feeding difficulties are prominent and lead to failure to thrive. Severe mental retardation and optic atrophy are constant features of the disease.
Low serum copper and ceruloplasmin levels have been found consistently in patients with Menkes disease, and a defect in copper absorption and transport across the gut has been shown to be the cause of the condition. Neuropathologic changes include tortuous degeneration of the gray matter, and marked changes in the cerebellum with loss of the internal granule cell layer and necrosis of the Purkinje cells.
Death occurs by 3yr of age in untreated patients.
Copper-histidine therapy has been shown to be effective in preventing neurologic deterioration in some patients with Menkes disease, particularly if treatment is begun during the neonatal period or, preferably, with the fetus. Copper is essential during the early stages of CNS development, and its absence probably accounts for the neuropathologic changes. Copper-histidine is given subcutaneously in a dose of 50-150mug elemental copper/kg/24hr for the duration of the child's life. The serum copper and ceruloplasmin levels return to the normal range within 2-3wk of commencing therapy. The occipital horn syndrome, a skeletal dysplasia caused by different mutations in the same gene as that involved in Menkes disease, is a relatively mild disease. The two diseases are often confused, because the biochemical abnormalities are identical. Resolution of the uncertainty about treatment of patients with Menkes disease will require careful genotype-phenotype correlation, along with further clinical trials of copper therapy.