A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report
<b>Background and Clinical Significance</b>: Aceruloplasminemia (ACP), a member of the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders, is a rare disorder caused by mutations in the ceruloplasmin (CP) gene. Iron accumulation in various organs, including the br...
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2024-12-01
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| author | Alexandros Giannakis Tsamis Konstantinos Maria Argyropoulou Georgia Xiromerisiou Spiridon Konitsiotis |
| author_facet | Alexandros Giannakis Tsamis Konstantinos Maria Argyropoulou Georgia Xiromerisiou Spiridon Konitsiotis |
| author_sort | Alexandros Giannakis |
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| description | <b>Background and Clinical Significance</b>: Aceruloplasminemia (ACP), a member of the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders, is a rare disorder caused by mutations in the ceruloplasmin (CP) gene. Iron accumulation in various organs, including the brain, liver, eyes, and heart, can lead to a broad clinical spectrum. Here, we report the first case of ACP in Greece. <b>Case Presentation</b>: Our patient was a 53-year-old male who was referred to our movement disorders center for a 6-month history of mild, unspecific, episodic dizziness and postural instability, and attention and memory deficits. Brain MRI revealed significant iron accumulation in multiple brain regions, including the dentate nuclei, cerebellar cortex, basal ganglia, thalamus, brainstem nuclei, and hypothalamus. These findings were particularly evident in susceptibility-weighted images. Fundoscopy revealed a normal retina, optic nerve, and macula. Whole-exome sequencing revealed a novel homozygous frameshift mutation in the CP gene [NM_000096.3:p.Thr3232fs (c.9695delC)]. This mutation has not been previously reported and is predicted to result in premature protein termination, supporting its pathogenic nature. Laboratory tests showed no anemia but revealed significantly elevated serum ferritin and low serum iron. Subsequent testing revealed extremely low serum CP and low serum copper. Despite less involvement of the myocardium, our patient succumbed to cardiac arrest. <b>Conclusions</b>: ACP should be considered in cases with minor neurological signs and symptoms. Brain MRI plays a significant role in early diagnosis. Close cardiac monitoring is also important. |
| format | Article |
| id | doaj-art-55b9539973454d338f7ac9dbf5671f83 |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-55b9539973454d338f7ac9dbf5671f832025-08-20T03:43:40ZengMDPI AGReports2571-841X2024-12-0181410.3390/reports8010004A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case ReportAlexandros Giannakis0Tsamis Konstantinos1Maria Argyropoulou2Georgia Xiromerisiou3Spiridon Konitsiotis4Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, GreeceDepartment of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, GreeceDepartment of Clinical Radiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, GreeceDepartment of Neurology, Faculty of Medicine, University Hospital of Thessaly, 45100 Larissa, GreeceDepartment of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece<b>Background and Clinical Significance</b>: Aceruloplasminemia (ACP), a member of the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders, is a rare disorder caused by mutations in the ceruloplasmin (CP) gene. Iron accumulation in various organs, including the brain, liver, eyes, and heart, can lead to a broad clinical spectrum. Here, we report the first case of ACP in Greece. <b>Case Presentation</b>: Our patient was a 53-year-old male who was referred to our movement disorders center for a 6-month history of mild, unspecific, episodic dizziness and postural instability, and attention and memory deficits. Brain MRI revealed significant iron accumulation in multiple brain regions, including the dentate nuclei, cerebellar cortex, basal ganglia, thalamus, brainstem nuclei, and hypothalamus. These findings were particularly evident in susceptibility-weighted images. Fundoscopy revealed a normal retina, optic nerve, and macula. Whole-exome sequencing revealed a novel homozygous frameshift mutation in the CP gene [NM_000096.3:p.Thr3232fs (c.9695delC)]. This mutation has not been previously reported and is predicted to result in premature protein termination, supporting its pathogenic nature. Laboratory tests showed no anemia but revealed significantly elevated serum ferritin and low serum iron. Subsequent testing revealed extremely low serum CP and low serum copper. Despite less involvement of the myocardium, our patient succumbed to cardiac arrest. <b>Conclusions</b>: ACP should be considered in cases with minor neurological signs and symptoms. Brain MRI plays a significant role in early diagnosis. Close cardiac monitoring is also important.https://www.mdpi.com/2571-841X/8/1/4aceruloplasminemianeurodegeneration with brain iron accumulationceruloplasminferritincase report |
| spellingShingle | Alexandros Giannakis Tsamis Konstantinos Maria Argyropoulou Georgia Xiromerisiou Spiridon Konitsiotis A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report Reports aceruloplasminemia neurodegeneration with brain iron accumulation ceruloplasmin ferritin case report |
| title | A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report |
| title_full | A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report |
| title_fullStr | A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report |
| title_full_unstemmed | A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report |
| title_short | A Novel Mutation Related to Aceruloplasminemia with Mild Clinical Findings: A Case Report |
| title_sort | novel mutation related to aceruloplasminemia with mild clinical findings a case report |
| topic | aceruloplasminemia neurodegeneration with brain iron accumulation ceruloplasmin ferritin case report |
| url | https://www.mdpi.com/2571-841X/8/1/4 |
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