Paula and Bobby
Parents of Lillie
What is Aceruloplasminemia?
Aceruloplasminemia is a rare disease. It is also known as Aceruloplasminemia Ceruloplasmin deficiency Systemic hemosiderosis.
A middle aged patient was described by Miyajima et al., (1987) who developed blepharospasm and a retinal degeneration. A CT scan showed areas of high density in the basal ganglia, and biochemically there was a deficiency of apoceruloplasmin associated with a low serum copper. Iron was reduced and accumulated in the liver, brain and pancreas. Other family members had the same biochemical defect and 2 had retinal changes. No-one else had the blepharospasm. A raised CSF iron concentration is a feature (Miyajima et al., 1998). MRI studies show marked hypointensity on T2-weighted images (Grisoli et al., 2005).
There have been reports of other families and the clinical picture is of an adult onset of chorea, athetosis and a cerebellar degeneration. In some it presents with an adult onset dementia (Harris et al., 1996), or even adult-onset diabetes (Takeuchi et al., 2002). The patient reported by Kohno et al., (2000), had a parkinsonian picture and diabetes. Haemers et al., (2004) reported a case who presented with perioral dyskinesia. Some develop a retinal degeneration. It is now clear that there are iron deposits in the brain and pancreas as well as the liver. Very long-chain fatty acid ratios are increased (Miyajima et al., 1998). The patient reported by Takeuchi et al., (2002), had an absence of serum ferroxidase activity, but ceruloplasmin was detectable in serum.
The gene has been mapped to 3q25 and a number of novel mutations have been identified (Yoshida et al., 1995 and Harris et al., 1995). A sib in the family reported by Takahashi et al.,(1996), had diabetes alone, whereas his sister had insulin dependent diabetes and a neurodegenerative disorder. The gene frequency in Japan is 70/100,000 (Miyajima et al., 1999). Heterozygotes might develop a cerebellar ataxia (Miyajima et al., 2001) or a mixture of ataxia and extrapyramidal features. The heterozygote reported by Jimenez-Huete et al., (2008), was ataxic, dysarthric and had cervical dystonia. Note the report by Yonekawa et al., (1999) of improvement after repeated administration of fresh-frozen plasma. The patient reported by Rusticeanu et al., (2014) had hepatic iron overload and diabetes but no neurological problems.
Vroegindeweij et al. (2016) reported two families and one unrelated patient with homozygous G631R mutation in the CP gene, but with broader clinical characteristics than the classical phenotype. The patients described, all Caucasian, predominantly had parkinsonism, cognitive decline and ataxia, while psychiatric changes and hyperkinetic movement disorder were less frequent. Neurological manifestations started above the fifth decade of life, with diverse features including behavioural changes, extrapyramidal symptoms and/or ataxia. Before the appearance of these symptoms anemia or diabetes was diagnosed in all the patients. Brain MRI, when available, showed iron deposits.
* This information is courtesy of the L M D.
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What gene changes cause Aceruloplasminemia?
The syndrome is inherited in the following inheritance pattern/s:
Autosomal Recessive - Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation that occurs during the reproductive process.
OMIM Number - 604290 (please check the OMIM page for updated information)
The syndrome can be caused by mutations in the following gene/s location/s:
CP - 3q24-q25
SLC40A1 - 2q32.2
What are the main symptoms of Aceruloplasminemia?
The typical symptoms of the syndrome are:
Scanning speech, Adult onset, Hypertonia, Hypothyroidism, Incoordination, Memory impairment, Neurological speech impairment, Tremor, Increased serum ferritin, Abnormality of iron homeostasis, Autosomal recessive inheritance, Torticollis, Retinopathy, Retinal degeneration, Abnormal renal physiology, Ataxia, Chorea, Behavioral abnormality, Blepharospasm, Anemia, Abnormality of extrapyramidal motor function, Cogwheel rigidity, Congestive heart failure, Dementia, Diabetes mellitus, Developmental regression, Dysarthria
How does someone get tested for Aceruloplasminemia?
The initial testing for Aceruloplasminemia can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
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