Aceruloplasminemia – What is this disease?
- Aceruloplasminemia is a rare condition of neurodegeneration with brain iron accumulation (NBIA).
- This condition is characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.
- This disorder is an adult onset one.
Epidemiology – What is the incidence?
- There have been reports of 56 cases of this disorder until date.
- The prevalence of this condition has been estimated at about 1/1,000,000-1/1,200,000.
What causes this condition?
- Aceruloplasminemia is caused by a complete absence of ceruloplasmin ferroxidase activity caused by homozygous mutation of the ceruloplasmin (CP) gene (3q23-q24).
What are the symptoms of Aceruloplasminemia?
Clinical description
- 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.
Very Frequent (common) symptoms
- Abnormal enzyme/coenzyme activity
- Abnormality of the nervous system
- Aceruloplasminemia
- Hypochromic microcytic anemia
- Increased circulating ferritin concentration
- Refractory anemia
Frequent (common) symptoms
- Abnormality of retinal pigmentation
- Ataxia
- Chorea
- Cognitive impairment
- Decreased circulating ceruloplasmin concentration
- Decreased circulating copper concentration
- Decreased serum iron
- Diabetes mellitus
- Dysarthria
- Dystonia
- Elevated hepatic iron concentration
- Gait ataxia
- Involuntary movements
- Limb ataxia
- Macular degeneration
- Retinal degeneration
Occasional symptoms
- Abnormal corpus striatum morphology
- Abnormal pancreas morphology
- Abnormal thalamic MRI signal intensity
- Abnormality of the dentate nucleus
- Akinesia
- Apathy
- Blepharospasm
- Congestive heart failure
- Craniofacial dystonia
- Facial grimacing
- Iron accumulation in brain
- Memory impairment
- Nystagmus
- Parkinsonism
- Rigidity
- Torticollis
- Tremor
How is this condition diagnosed?
Diagnostic methods
- Lab work – This condition is diagnosed 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.
- The confirmatory diagnosis is Genetic testing.
Differential 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
- Drug effects or toxicity
Antenatal diagnosis
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.
Genetic counseling
Aceruloplasminemia is inherited in an autosomal recessive manner.
Management and treatment – How is this disorder treated?
- Treatment is based on intravenous and oral iron chelators (deferiprone or deferasirox). These agents 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.
What is the prognosis of this condition?
- This disease might lead to heart failure due to cardiac iron overload.
- As per the recent statistics estimation five patients with aceruloplasminemia are known to have died in their sixties. The most probable reason is due to from heart failure resulting from cardiac iron overload.
- There is a good prognosis with good treatment of diabetes and in the absence of heart failure.
