Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Aceruloplasminemia

ORPHA48818
Synonym(s) Hereditary ceruloplasmin deficiency
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Adult
ICD-10
  • G23.0
OMIM
UMLS -
MeSH
  • C536004
MedDRA -

Summary

Aceruloplasminemia is an adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.

To date 56 cases have been reported and prevalence has been estimated at about 1/1,000,000-1/1,200,000.

Aceruloplasminemia presents in adulthood with neurological symptoms including ataxia, involuntary movements (blepharospasm, grimacing, facial and neck dystonia, tremors, and chorea), parkinsonism, depression, and cognitive dysfunction accompanied by retinal degeneration, diabetes mellitus, and iron-refractory anemia.

Aceruloplasminemia is caused by a complete absence of ceruloplasmin ferroxidase activity caused by homozygous mutation of the ceruloplasmin (CP) gene (3q23-q24).

Diagnosis is based on the absence of serum ceruloplasmin and some combination of low serum copper concentration, low serum iron concentration, high serum ferritin concentration as well as hepatic iron overload. The diagnosis is strongly supported by characteristic MRI findings of abnormal low intensities reflecting iron accumulation on the brain (striatum, thalamus, dentate nucleus) and liver on both T1- and T2- weighted images. Genetic testing can confirm the diagnosis.

Differential diagnoses include other forms of later-onset, slowly progressing NBIA including atypical pantothenate kinase-associated neurodegeneration (PKAN) and neuroferritinopathy, hereditary hemochromatosis, Wilson disease, Huntington disease, dentatorubral pallidoluysian atrophy (DRPLA), juvenile Parkinson disease, hereditary spinocerebellar ataxias (see these terms) and drug effects or toxicity.

Prenatal testing for pregnancies at increased risk may be available through laboratories offering custom prenatal testing if the disease-causing mutations have been identified in an affected family member.

Aceruloplasminemia is inherited in an autosomal recessive manner.

Treatment is based on intravenous and oral iron chelators (deferiprone or deferasirox), which have been associated with improvement in diabetes and neurological symptoms. Combined IV desferrioxamine and fresh-frozen human plasma (FFP) is effective in decreasing iron content in the liver. Antioxidants such as vitamin E and oral administration of zinc may prevent tissue damage.

Prognosis may include heart failure due to cardiac iron overload. To date five patients with aceruloplasminemia are known to have died from heart failure probably due to cardiac iron overload in their sixties. In the absence of heart failure and with good treatment of diabetes, the prognosis is good.

Expert reviewer(s)

  • Dr Hiroaki MIYAJIMA

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image

Detailed information

Clinical genetics review
  • EN (2013)
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.