Iron in the Hallervorden-Spatz syndrome.
The dark discoloration of globus pallidus and substantia nigra pars reticularis in the Hallervorden-Spatz syndrome is due to the accumulation of iron. Routine iron stains detect the metal mostly in microglia and macrophages, but scattered neurons are also reactive. Axonal spheroids are characteristic of the disease, and many of these expansions give a positive iron reaction. Globus pallidus and substantia nigra are normally rich in iron, and additional "storage" of the metal has often been considered the essential factor in the pathogenesis of Hallervorden-Spatz syndrome. However, other equally iron-rich structures, such as the red nucleus and the dentate nucleus, remain unaffected. In normal globus pallidus and substantia nigra pars reticularis, double-label immunofluorescence microscopy of ferritin, as an indirect marker of cellular iron localization, and phosphorylated neurofilament protein reveal close proximity of ferritin-reactive microglial and oligodendroglial processes to tightly packed axons. It is proposed that a primary axonal disorder allows the seepage of iron into the axoplasm. Iron may contribute to the axonal disease, but accumulation of the metal probably should be viewed as an epiphenomenon. Pallidal and nigral iron excess is not unique to Hallervorden-Spatz syndrome, and some previously reported postmortem examinations may actually represent pallidonigroluysian atrophy.
Koeppen
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AH
Neurology Services, VA Medical Center, Albany, NY 12208, USA.
Dickson
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AC
D002648:Child; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000032:analysis*; D008667:Metalloproteins / Q000032:analysis; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*
D008667:Metalloproteins; D007501:Iron