Session Information
Date: Tuesday, June 6, 2017
Session Title: Rare Genetic and Metabolic Diseases
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: We describe the phenotype of a novel ceruloplasmin mutation and the neurological response to different iron-chelating therapies.
Background: Aceruloplasminemia (AC) is a rare autosomal recessive disorder of iron metabolism, caused by lack of ceruloplasmin ferroxidase activity subsequent to mutations in ceruloplasmin gene. AC is characterized by anemia, low serum iron, high serum ferritin and iron accumulation in the liver, pancreas, brain and other tissues. Neurological manifestations include parkinsonism, ataxia, cognitive dysfunction and involuntary movements. Till now, the therapeutic strategy is not standardized.
Methods: Case report.
Results: A pair of brothers presented with anemia, hyperferritinemia, low serum iron, copper and ceruloplasmin, low urinary copper, diabetes and neuropsychiatric involvement. The older brother suffered from hypertransaminasemia and primary hypothyroidism. Neurological examination (NE) showed facial hypomimia, neck dystonia, bradykinesia, rigidity, ataxia, pyramidal signs and oro-mandibular dyskinesias. Archaic reflexes were also present. The younger showed axonal polyneuropathy, arthrosis and chondrocalcinosis. NE revealed mild distal sensory loss and lower limbs areflexia. Neuropsychological tests showed in both impairment in praxis and constructive abilities, executive functions and anterograde memory. MRI studies revealed iron accumulation in the liver and pancreas; liver biopsy confirmed hepatocellular siderosis and fibrosis. Brain MRI showed overload of paramagnetic material in dentatus, putamen, posterior talamus, cortical grey matter and pituitary gland, associated with brain atrophy. Ceruloplasmin gene sequencing found a novel c.2242C>T, p.Gln748*. Iron-chelation program with deferoxamine and then with deferiprone was without benefits. Finally, low doses (5 mg/kg) of deferasirox leading to normalization of liver iron content with significant motor improvement in the older brother and normalization of neuropsychological assessment in both.
Conclusions: These cases highlight the diagnostic complexity of AC, characterized by variable genotype-phenotype correlation. Long term-low doses iron chelation with deferasirox was able to restore normal liver iron content and to improve significantly the neuropsychological and motor performances.
References:
- McNeill A, Pandolfo M, Kuhn J, Shang H, Miyajima H.The neurological presentation of ceruloplasmin gene mutations. Eur Neurol. 2008;60(4):200-205.
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Bove F, Fasano A. Iron chelation therapy to prevent the manifestations of aceruloplasminemia. Neurology. 2015;85(12):1085-1086.
To cite this abstract in AMA style:
F. Valzania, F. Cavallieri, M. Fiorini, S. Contardi, F. Ferrara, E. Menozzi, S. Scarlini, F. Cavalleri, M. Molinari, A. Pietrangelo, E. Corradini. A Pair of Brothers with Aceruloplasminemia Due to a Novel Nonsense Mutation: Unusual Phenotype and Neurological Improvement After Iron-Chelation Therapy with Deferasirox. [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/a-pair-of-brothers-with-aceruloplasminemia-due-to-a-novel-nonsense-mutation-unusual-phenotype-and-neurological-improvement-after-iron-chelation-therapy-with-deferasirox/. Accessed June 14, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-pair-of-brothers-with-aceruloplasminemia-due-to-a-novel-nonsense-mutation-unusual-phenotype-and-neurological-improvement-after-iron-chelation-therapy-with-deferasirox/