Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.
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PMID:Clinical and biochemical consequences of copper-histidine therapy in Menkes disease. 822 85

The primary mechanism of copper transport to the brain is unknown, although this process is drastically impaired in Menkes disease, an X-linked neurodevelopmental disorder caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Potential central nervous system entry routes for copper include brain capillary endothelial cells that originate from mesodermal angioblasts and form the blood-brain barrier, and the choroid plexuses, which derive from embryonic ectoderm, and form the blood-cerebrospinal fluid barrier. We exploited a rare (and first reported) example of somatic mosaicism for an ATP7A mutation to shed light on questions about copper transport into the developing brain. In a 20-month-old Menkes disease patient evaluated before copper treatment, blood copper, and catecholamine concentrations were normal, whereas levels in cerebrospinal fluid were abnormal and consistent with his neurologically severe phenotype. We documented disparate levels of mosaicism for an ATP7A missense mutation, P1001L, in tissues derived from different embryonic origins; allele quantitation showed P1001L in approximately 27% of DNA samples from blood cells (mesoderm-derived) and 88% from cultured fibroblasts (ectoderm-derived). These findings imply that the P1001L mutation in the patient preceded formation of the three primary embryonic lineages at gastrulation, with the ectoderm layer ultimately harboring a higher percentage of mutation-bearing cells than mesoderm or endoderm. Since choroid plexus epithelia are derived from neuroectoderm, and brain capillary endothelial cells from mesodermal angioblasts, the clinical and biochemical findings in this infant support a critical role for the blood-CSF barrier (choroid plexus epithelia) in copper entry to the developing brain.
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PMID:Somatic mosaicism in Menkes disease suggests choroid plexus-mediated copper transport to the developing brain. 2079 18