A parkinsonian movement disorder with brain iron deposition and a haemochromatosis mutation

Sa, Williams; Vinjam, Maruthi; Ismail, Azzam; Hassan, Ahamad

doi:10.1007/s00415-013-6995-y

Cited by 6 publications

(11 citation statements)

References 8 publications

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“…We further investigated other monoamine transporters that affect extracellular monoamine levels. While SERT is involved in regulating emotional behavior (Canli and Lesch, 2007; Williams et al, 2013), we observed that Mn-induced impulsivity could be associated with increased expression of SERT in the striatum, which appears parallel to a finding that SERT deficiency exhibits anxiogenic effect in mice (Holmes et al, 2003). While iron deficiency has been shown to down-regulate brain NET (Beard et al, 2006; Burhans et al, 2005), our study demonstrates that loss of Hfe function increases NET, which would decrease extracellular concentration of norepinephrine.…”

Section: Discussionsupporting

confidence: 74%

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

Kim

2015

Environmental Toxicology and Pharmacology

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Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe−/− mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe−/− mice. Compared with manganese-instilled wild-type mice, Hfe−/− mice showed decreased manganese accumulation in the cerebellum. Hfe−/− mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation.

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Section: Discussionsupporting

confidence: 74%

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

Kim

2015

Environmental Toxicology and Pharmacology

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“…15,16 This view was supported by the postmortem finding in HH patients with iron deposition in the choroid plexus without any abnormal basal ganglia pigmentation, 3,17 however, Williams et al reported postmortem iron deposition in the basal ganglia, locus coeruleus, and dentate nuclei in a case of HH with parkinsonism related to multiple system atrophy, parkinsonian type. 13 Iron deposition in the basal ganglia and cerebellum may cause movement disorders in HH. 11 The reason for the susceptibility of the basal ganglia to iron deposition is not well-understood, but it may be related to selective neuronal uptake and abnormal vascular or axonal transport along white matter tracts connecting these nuclei.…”

Section: Discussionmentioning

confidence: 99%

“…12 Few cases had normal MRI scans. 8,9,13 One author describes six patients with systemic HH without neurological manifestations, but with neuroimaging findings suggestive of iron deposition. 19 This underlines the difficulty in correlating the neurological features and brain iron deposition in HH patients.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic abnormalities in HFE and related proteins may affect the blood-brain barrier in few patients with HH, leaving their brain devoid of this protection. 13 Thus, the HFE gene mutations are considered to be the prime contributor of iron overload in the brain of HH patients, 15,20 thereby increasing the risk of neurodegenerative disorders. 15,16,21 In addition to the homozygous HFE mutation (C282Y), the NGS showed an associated mutation in the CDAN1 gene in patient 1 and HAMP gene in patient 2.…”

Section: Discussionmentioning

confidence: 99%

“…1 HH usually does not involve the nervous system, with even fewer reported cases presenting with movement disorders. [3][4][5][6][7][8][9][10][11][12][13] We describe three HH patients affected by isolated movement disorders without any other major systemic features of HH and review the literature with an aim to explore a possible causal relationship between HH and neurological manifestations.…”

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confidence: 99%

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Movement Disorders Associated With Hemochromatosis

Kumar

Rizek

Sadiković

et al. 2016

Can. J. Neurol. Sci.

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Background: Hereditary hemochromatosis (HH) is a genetic disorder causing pathological iron deposition and functional impairment of various organs, predominantly the liver. We assessed patients with HH for the presence of movement disorders. Methods: We reviewed the charts of 616 patients with HH who attended hemochromatosis clinic at London Health Sciences Centre, London, ON, Canada, from 1988 to 2015. Results: We found three HH patients with movement disorders, without any other major systemic manifestation. One had parkinsonism, another had chorea, and the third had tremor. All three patients had evidence of iron deposition in the brain, affecting the basal ganglia in the first two, and the dentate nucleus, red nucleus, and substantia nigra in the third patient. In addition to the C282Y homozygous mutation in the HFE gene, two of our patients had non-HFE gene mutations. Conclusion: HH should be considered in the differential diagnosis of movement disorders with pathological brain iron deposition. We report for the first time chorea in a patient with HH. Non-HFE gene mutations may predispose HH patients to iron deposition in the brain.RÉSUMÉ: Troubles du mouvement associés à l'hémochromatose. Contexte : L'hémochromatose héréditaire (HH) est une maladie génétique qui entraîne des dépôts pathologiques de fer et des altérations fonctionnelles au niveau de différents organes, particulièrement au niveau du foie. Nous avons examiné la présence de troubles du mouvement chez des patients atteints de HH. Méthodologie : Nous avons revu les dossiers de 616 patients atteints de HH traités à la clinique d'hémochromatose du London Health Sciences Centre de London, Ontario, Canada, de 1988 à 2015. Résultats : Nous avons identifié 3 patients atteints de HH qui présentaient des troubles du mouvement sans autre manifestation systémique importante. Un patient présentait du parkinsonisme, un autre de la chorée et le troisième du tremblement. Ces trois patients avaient des dépôts de fer dans le cerveau, soit au niveau des noyaux gris centraux chez les deux premiers et dans le noyau dentelé, le noyau rouge et le locus niger chez le troisième patient. En plus de la mutation homozygote C282Y dans le gène HFE, deux de nos patients avaient des mutations génétiques qui n'étaient pas dans le gène HFE. Conclusion : L'HH devrait être incluse dans le diagnostic différentiel des troubles du mouvement chez les patients qui présentent des dépôts pathologiques de fer dans le cerveau. Nous rapportons pour la première fois de la chorée chez un patient atteint d'HH. Des mutations dans des gènes autres que HFE pourraient prédisposer les patients atteints d'HH à la formation de dépôts de fer dans le cerveau.

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Movement Disorders and Hematologic Diseases

Patel

Hall

Eichenseer

et al. 2020

Movement Disord Clin Pract

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BackgroundMovement disorders can be associated with or caused by hematological abnormalities. The objective of this review is to highlight features that will aid in the clinician's recognition and treatment of these disorders.MethodsMESH terms relevant to movement disorders and hematologic diseases were searched to identify conditions included in this narrative, educational review.ResultsSeveral conditions were identified, and they were organized by hematologic categories to include red blood cell abnormalities, white blood cell abnormalities, disorders of clotting and bleeding, hematologic malignancies, and others.ConclusionsThis review will increase providers’ understanding of disorders that include movement disorders and hematologic abnormalities. Basic hematologic laboratories can aid in assessment of these disorders, to include complete blood count/hemogram and peripheral blood smear. Recognition is key, especially in the setting of underlying malignancy, vitamin deficiency, or other disorder in which treatment is available.

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A parkinsonian movement disorder with brain iron deposition and a haemochromatosis mutation

Cited by 6 publications

References 8 publications

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

Movement Disorders Associated With Hemochromatosis

Movement Disorders and Hematologic Diseases

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