Disturbances in copper metabolism caused by mutations in the ATP7A/Atp7a gene lead to severe metabolic syndromes Menkes disease in humans and the lethal mottled phenotype in mice.
While the spectrum of mutations detected in the Atp7a murine gene provides an explanation for at least part of the wide phenotypic variation observed in mottled mutant mice, there is a singular absence of deletions which are associated with a sizeable fraction of human Menkes syndrome cases.
Genomic DNA of 41 unrelated patients affected with the classical severe form of Menkes disease was investigated for point mutations in the ATP7A gene (previously designated as the "MNK" gene).
Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter.
The essential requirement for copper in early development is dramatically illustrated by Menkes disease, a fatal neurodegenerative disorder of early childhood caused by loss-of-function mutations in the gene encoding the copper transporting ATPase ATP7A.
Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.
Menkes disease (MD), an X-linked recessive disorder of copper metabolism caused by mutations in the copper-transporting ATP7A gene, results in growth failure and severe neurodegeneration in early childhood.
Based on review of X-inactivation patterns in female carriers of other X-linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A-related distal motor neuropathy.
Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter.
We describe a child with classical Menkes disease with a novel ATP7A mutation, intractable seizures, severe hypotonia and developmental delay, hypopigmentation of the skin and hair, and failure to thrive, who was treated with daily subcutaneous copper histidine injections for 2(1/2) years, beginning at 15 months of age.