Hereditary ceruloplasmin deficiency with hemosiderosis: A clinicopathological study of a japanese family

Abstract

A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus, all of which appeared when they were between 30 and 50 years old. All had serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The dentate nucleus, thalamus, putamen, caudate nucleus, and liver of each one showed low signal intensities on T1- and T2-weighted magnetic resonance images. Examination of the central nervous system revealed severe destruction of the basal ganglia and dentate nucleus, with considerable iron deposition in neuronal and glial cells, whereas the cerebral cortex showed mild iron deposition in glial cells without neuronal involvement. An electron microscopic study with energy-dispersive x-ray analysis showed iron depositions in the hepatocytes, of both the neural and glial cells of the brain. We consider this a new disease entity because of the primary ceruloplasmin deficiency.

Ceruloplasmin Ferroxidase Activity Stimulates Cellular Iron Uptake by a Trivalent Cation-specific Transport Mechanism

“…The data presented here and elsewhere suggest that alterations in plasma Cp concentration or activity may alter iron homeostasis, and could contribute to human disease. The finding of hemochromatosis in aceruloplasminemia patients is generally considered as evidence that the normal function of Cp is to mediate iron efflux from cells and tissues (47,48). However, these studies may also be consistent with a role of Cp in cellular iron uptake.…”

Aceruloplasminemia with Juvenile-onset Diabetes Mellitus Caused by Exon Skipping in the Ceruloplasmin Gene

“…Aceruloplasminemia is a disorder of iron metabolism that is characterized by excessive iron deposition in various organs such as the brain, liver and pancreas (7). Clinical manifestations of aceruloplasminemia include diabetes mellitus, retinal degeneration and neurological abnormalities (3)(4)(5)(6).…”

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

“…These patients have pathologic accumulation of iron in liver, spleen, pancreas, retina, and basal ganglia by the fourth or fifth decade of life (5,6). Five Japanese patients all had pigmentary retinopathy by their fifth decade (5)(6)(7).…”

“…Five Japanese patients all had pigmentary retinopathy by their fifth decade (5)(6)(7). Although histopathology has not been published, one patient had retinal iron overload in unspecified cell types (6). One Caucasian patient with undetectable serum ceruloplasmin had drusen, yellowish white spots under the retina that constitute the defining clinical feature of AMD (J.L.D., unpublished results).…”