Aceruloplasminemia


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Aceruloplasminemia

A neurodegenerative disorder characterised by accumulation of iron in the brain and a clinical triad of retinal degeneration, diabetes mellitus, and neurologic signs/symptoms.
Clinical findings Movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and cerebellar ataxia (gait ataxia, dysarthria), progressive extrapyramidal signs, and dementia
Lab Absent serum ceruloplasmin due to a mutation in the ceruloplasmin gene and one or more of the following: low serum copper or iron, high serum ferritin, and increased iron in the glia, neurones, basal ganglia and dentate nucleus, liver cells, and pancreatic islets.
Imaging MRI findings of abnormal low intensities reflecting iron accumulation in the brain (striatum, thalamus, dentate nucleus) and liver on both T1- and T2-weighted images.
Management Chelation with desferrioxamine, fresh-frozen plasma (FFP) to reduce iron in the liver may improve neurologic signs/symptoms; antioxidants (vitamin E), zinc and deferasirox (iron chelator) may prevent hepatic and pancreatic damage.
References in periodicals archive ?
Decreased concentrations of ceruloplasmin may indicate aceruloplasminemia, Menkes disease, or Wilson disease.
Several hereditary disorders, including aceruloplasminemia, can disrupt this homeostasis.
Aceruloplasminemia is an autosomal recessive disorder characterized by a lack of ceruloplasmin ferroxidase activity important for iron conversion and exportation.
5) The unique involvement of the central nervous system (CNS) distinguishes aceruloplasminemia from other iron or paramagnetic element storage disorders including hemochromatosis, Hallervorden-Spatz, and Wilson's disease.
Studies from an IRP deficient murine model suggests that impairment of ferritin transcriptional regulation result in iron accumulation in oligodendrocytes leading to neuronal degeneration and secondary iron deficiency similar to aceruloplasminemia (69).
Astrocyte deformity and globular structures are characteristic of the brain patients with aceruloplasminemia.
Iron-overload and antioxidative role of perivascular astrocytes in aceruloplasminemia.
OS resulting from perturbations in the levels or distribution of brain Fe and Cu has been implicated in an impressive array of genetic and acquired neurological disorders, including such entities as Friedreich ataxia, pantothenate kinase-2-associated neurodegeneration (formerly Hallervorden-Spatz disease), neuroferritinopathy, Alzheimer disease, Parkinson disease, multiple sclerosis, aceruloplasminemia, superficial siderosis, the restless legs syndrome, and Wilson disease.
Ceruloplasmin deficiency also has been observed in other pathological conditions, including Menkes disease, protein calorie malnutrition, nephrotic syndrome, protein-losing enteropathy, acquired copper deficiency, and hereditary aceruloplasminemia (31).
Differential diagnosis should also include familial hyperferritinemia congenital cataract syndrome (HHCS), which is a rare disease without iron overload but with high ferritin concentrations (134,135); aceruloplasminemia, which manifests predominately with neurologic symptoms (136,137); and the increasingly prevalent metabolic syndrome present in obese, hypertensive, insulin-resistant, or dyslipidemic individuals (Table 1) (39,43).
In hereditary cases of iron overload in the presence of isolated hyperferritinemia, the differential diagnosis should include hypotransferrinemia and aceruloplasminemia.
This chapter also introduces the major genetic disorders of copper metabolism: Menkes and Wilson diseases and aceruloplasminemia.