Idiopathic brain calcification in a patient with hereditary hemochromatosis.


Journal

BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555

Informations de publication

Date de publication:
30 Mar 2020
Historique:
received: 23 07 2019
accepted: 17 03 2020
entrez: 2 4 2020
pubmed: 2 4 2020
medline: 18 8 2020
Statut: epublish

Résumé

Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D-PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.

Sections du résumé

BACKGROUND BACKGROUND
Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported.
CASE PRESENTATION METHODS
A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D-PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative.
CONCLUSIONS CONCLUSIONS
This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.

Identifiants

pubmed: 32228506
doi: 10.1186/s12883-020-01689-1
pii: 10.1186/s12883-020-01689-1
pmc: PMC7106592
doi:

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113

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Auteurs

Stefania Scarlini (S)

Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Francesco Cavallieri (F)

Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia, Italy.
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.

Massimo Fiorini (M)

Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Elisa Menozzi (E)

Department of Neuroscience, S. Agostino-Estense Hospital, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Francesca Ferrara (F)

Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Francesca Cavalleri (F)

Department of Neuroradiology, Policlinico|, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.

Chiara Reale (C)

Medical Genetics and Neurogenetics Unit, Movement Disorders Diagnostic Section, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.

Barbara Garavaglia (B)

Medical Genetics and Neurogenetics Unit, Movement Disorders Diagnostic Section, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.

Antonello Pietrangelo (A)

Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Franco Valzania (F)

Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia, Italy. franco.valzania@ausl.re.it.

Elena Corradini (E)

Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

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