Last revised by Rohit Sharma on 23 Feb 2024

Aceruloplasminemia is an autosomal recessive type of neurodegeneration with brain iron accumulation and disorder of iron metabolism caused by a mutation in the ceruloplasmin (CP) gene resulting in the production of dysfunctional ceruloplasmin.

Aceruloplasminemia is a very rare disorder, with one Japanese study estimating a prevalence of approximately 1 in 2 million 1. The disease became symptomatic in an age group of 20 to 60 years 1.

Patients present with a classic triad of clinical features caused by iron accumulation in various organs: 

  • neurologic disease: movement disorders, ataxia, eventual cognitive impairment 2-4

  • diabetes mellitus 2-4

  • retinal degeneration: usually visual acuity is not affected but changes can be appreciated on fundoscopy 2-4

In addition to this classic triad, most patients also have iron deficiency anemia which may or may not be symptomatic depending on its severity 2-4.

Aceruloplasminemia is an autosomal recessive disorder caused by a mutation in the CP gene on the long arm of chromosome 3 resulting in the production of dysfunctional ceruloplasmin 5,6. Ceruloplasmin normally has a role in oxidising ferrous iron into its ferric form, allowing it to be loaded onto transferrin after being released by ferroportin 5,6. In patients with aceruloplasminemia, dysfunctional ceruloplasmin results in dysfunctional transport of iron out of cells around the body, causing iron accumulation and subsequent damage within those cells and tissues 5,6.

This iron accumulation typically occurs in three locations 5,6:

In addition to these three locations, the liver is also commonly involved asymptomatically, as well as other organs such as the heart or kidneys which are less commonly affected 5,6.

In general, radiographic changes are appreciated in the brain and the liver 6-9.

CT may reveal abnormal hyperdensities in the liver and brain, typically in the basal ganglia 6.

MRI is the modality of choice for evaluating patients with aceruloplasminemia 7-9. Signal changes are most commonly described in the brain and liver, and include 7-9:

Being a more sensitive imaging modality compared to CT for this condition, an often more extensive disease is noted, particularly in brain imaging where not only are the basal ganglia involved, but signal changes are also appreciated in the thalamuscerebral cortex, and cerebellum (especially the dentate nucleus7-9

Treatment is with iron chelation therapy, using agents such as desferrioxamine 10. These agents have been shown to prevent progression of neurologic clinical features 10.

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