Endocrine Abnormalities in a Case of Neurodegeneration with Brain Iron Accumulation

Haeri, Ghazal; Akhoundi, Fahimeh Haji; Alavi, Afagh; Abdi, Salman; Rohani, Mohammad

doi:10.1002/mdc3.12990

Cited by 3 publications

(3 citation statements)

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“…110 The first only case of WSS in Iran has also been reported recently. 91 Also, we found one case of FAHN and a family affected by aceruloplasminemia with two affected siblings who have not been reported yet. There are no reports of neuroferritinopathy and CoPAN in the Iranian population so far, meaning that these forms are very rare (Table 1).…”

Section: Nbia In Iranmentioning

confidence: 63%

“…Respectively, there were 23, 5, 3, 1, 3, 3, and one family with PKAN, MPAN, PLAN, JABELS, BPAN, Kufor-Rakeb and WSSs in Iran (Figure 4). 74,[91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109] Like the other countries, the most common form of NBIA was PKAN accounting for more than half of the cases (59%) (Figure 4). A high percentage of the PKAN may be due to the easy diagnostics procedures; the specific pattern on MRI, which is the "eye of tiger" sign.…”

Section: Nbia In Iranmentioning

confidence: 99%

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Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

Hajati

Emamikhah

Fard

et al. 2021

Can. J. Neurol. Sci.

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Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals. Current therapies are exclusively symptomatic and unable to hinder the disease progression. Approximately 16 genes have been identified and affiliated to such condition with different functions such as iron metabolism (only two genes: Ferritin Light Chain (FTL) Ceruloplasmin (CP)), lipid metabolism, lysosomal functions, and autophagy process, but some functions have remained unknown so far. Subgroups of NBIA are categorized based on the mutant genes. Although in the last 10 years, the development of whole-exome sequencing (WES) technology has promoted the identification of disease-causing genes, there seem to be some unknown genes and our knowledge about the molecular aspects and pathogenesis of NBIA is not complete yet. There is currently no comprehensive study about the NBIA in Iran; however, one of the latest discovered NBIA genes, GTP-binding protein 2 (GTPBP2), has been identified in an Iranian family, and there are some patients who have genetically remained unknown.

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Section: Nbia In Iranmentioning

confidence: 63%

Section: Nbia In Iranmentioning

confidence: 99%

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

Hajati

Emamikhah

Fard

et al. 2021

Can. J. Neurol. Sci.

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“…Other rare genetic disorders were suggested to belong to the NBIA group, mostly based on brain MRI findings, i.e., decreased basal ganglia signal on T2/T2* or susceptibility weighted images (reviewed in [239]): Fatty acid 2 hydroxylase-associated neurodegeneration [240], Woodhouse-Sakati syndrome caused by mutations in DCAF17 gene [241,242], Kufor-Rakeb syndrome caused by ATP13A2 mutations [243,244], Adaptor protein complex 4 (AP4) deficiency [245], sterol carrier protein 2 (SCP2) deficiency [246], DDHD1 encoding phospholipase A1 [247], FBXO7 deficiency [248], GTP-binding protein 2 (GTPBP2) deficiency [249,250], fucosidosis [251], GM1 gangliosidosis [252], VAC14 syndrome [253], and TBCE [254], KMT2B [255], IRF2BPL [256], REPS1, and CRAT mutations [182]. Further research into brain Fe homeostasis in these disorders may generate important information regarding mechanisms and consequences of brain Fe disturbances.…”

Section: Neurodegenerations With Brain Iron Accumulation (Nbia) Groupmentioning

confidence: 99%

Cerebral Iron Deposition in Neurodegeneration

et al. 2022

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Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson’s disease, Friedreich’s disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood–brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.

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Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review

Kohil

Abdallah

Hussain

et al. 2023

Orphanet J Rare Dis

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Background Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease. Methods PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are “Woodhouse Sakati” along with the term “mutation” OR “gene” OR “variant” OR “polymorphism”. Results Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype–phenotype correlations for the different variants. Conclusions This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype–phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients.

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Endocrine Abnormalities in a Case of Neurodegeneration with Brain Iron Accumulation

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Cited by 3 publications

References 5 publications

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

Cerebral Iron Deposition in Neurodegeneration

Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review

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