Menkes' disease is an X-linked disorder caused by impaired intracellular transport of
copper. Currently, no
therapy effectively arrests the relentless neurodegeneration of
Menkes' disease. Previous neuroimaging reports of patients with
Menkes' disease describe a range of abnormalities, including intracranial vessel tortuosity and cerebral white matter changes. We report two infants with
Menkes' disease who developed ischemic
cerebrovascular disease early in infancy. Magnetic resonance studies, including diffusion-weighted imaging and
proton magnetic resonance spectroscopy, demonstrated bilateral
infarctions of deep gray matter nuclei, a finding not previously described in
Menkes' disease. Potential mechanisms for these cerebrovascular lesions in
Menkes' disease include the susceptibility to
free radical attack and inadequate energy supply from oxidative phosphorylation. These
infarctions may play an unrecognized but important role in the neurodegeneration of children with
Menkes' disease. The development of effective therapeutic agents against this disease will require a more detailed understanding of such underlying mechanisms.