Consensus clinical management guideline for beta‐propeller protein‐associated neurodegeneration

Wilson, Jenny; Gregory, Allison; Kurian, Manju A.; Bushlin, Ittai; Mochel, Fanny; Emrick, Lisa; Adang, Laura; Hogarth, Penelope; Hayflick, Susan J.; Rogers, Caleb; Lee, Jae‐Hyeok; Burke, Kimberly Gladden; Dyer, Meg Tally; Stretter, Donna

doi:10.1111/dmcn.14980

Cited by 33 publications

(30 citation statements)

References 31 publications

(81 reference statements)

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“…There was no clinical evidence of hemolytic anemia in this patient. Even if hemolysis is not macroscopically observed in vitro, invisible hemolysis may remained of uncertain significance (Wilson et al, 2021). One of the limitations of this study was that it is a single case report.…”

Section: Discussionmentioning

confidence: 92%

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Time course of serum neuron‐specific enolase levels from infancy to early adulthood in a female patient with beta‐propeller protein‐associated neurodegeneration

Hirano

Suzuki

Ikeda

et al. 2023

American J of Med Genetics Pt A

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Beta‐propeller protein‐associated neurodegeneration (BPAN), a subgroup of neurodegeneration with brain iron accumulation, is typically characterized by non‐progressive global developmental delay and seizures in childhood, followed by progressive neurological decline with parkinsonism and dementia in adolescence or early adulthood. It is difficult to clinically identify a patient with BPAN in childhood. Recent studies reported that serum levels of neuron‐specific enolase (NSE) were elevated in children with BPAN. We reviewed the time course of serum NSE levels in a 21‐year‐old female patient genetically diagnosed (a de novo WDR45 variant c.268A > T) with BPAN, which was suspected based on prolonged elevation of serum NSE. There was an overall tendency for serum NSE levels to decrease in a stepwise fashion. The peak serum NSE level was observed during the first 2 years of age and then decreased rapidly in 1 year. High serum NSE levels persisted between 3 and 11 years of age. Subsequently, serum NSE levels decreased and plateaued after 13 years of age. There were tendencies for both blood AST and LDH levels to decrease over time in parallel with serum NSE levels. Serum NSE levels may be a diagnostic biomarker of BPAN in children but becomes of less value in identifying a patient with BPAN after childhood.

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Section: Discussionmentioning

confidence: 92%

“…Recently published clinical management guideline for BPAN indicated that the diagnostic biomarker of these laboratory tests remained of uncertain significance (Wilson et al, 2021). One of the limitations of this study was that it is a single case report.…”

Section: Discussionmentioning

confidence: 99%

Time course of serum neuron‐specific enolase levels from infancy to early adulthood in a female patient with beta‐propeller protein‐associated neurodegeneration

Hirano

Suzuki

Ikeda

et al. 2023

American J of Med Genetics Pt A

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“…BPAN (OMIM #300894) manifests as global developmental delay with epilepsy and Rett-like syndrome in childhood and rapid-onset dystonia-parkinsonism and progressive dementia in early adulthood (recently reviewed in [224][225][226]). The WD-domain repeat 45 (WDR45) gene encode a beta-propeller WD repeat protein interacting with phosphoinositides (WIPI4), which is critically involved in the autophagosome-lysosome fusion in neuronal cells [227].…”

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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“…Other reported features include behavioral problems, sleep disorders, and ophthalmological abnormalities (Gregory et al, 1993;Hayflick et al, 2013). A consensus clinical management guideline for BPAN was recently published (Wilson et al, 2021). Besides BPAN, other phenotypes associated with variants in WDR45 include Rett-like syndrome, intellectual disability, developmental and epileptic encephalopathy and West syndrome (Cong et al, 2021).…”

Section: Wipi (Wdr )mentioning

confidence: 99%

WIPI proteins: Biological functions and related syndromes

Almannai

Marafi

El‐Hattab

2022

Front. Mol. Neurosci.

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WIPI (WD-repeat protein Interacting with PhosphoInositides) are important effectors in autophagy. These proteins bind phosphoinositides and recruit autophagy proteins. In mammals, there are four WIPI proteins: WIPI1, WIPI2, WIPI3 (WDR45B), and WIPI4 (WDR45). These proteins consist of a seven-bladed β-propeller structure. Recently, pathogenic variants in genes encoding these proteins have been recognized to cause human diseases with a predominant neurological phenotype. Defects in WIPI2 cause a disease characterized mainly by intellectual disability and variable other features while pathogenic variants in WDR45B and WDR45 have been recently reported to cause El-Hattab-Alkuraya syndrome and beta-propeller protein-associated neurodegeneration (BPAN), respectively. Whereas, there is no disease linked to WIPI1 yet, one study linked it neural tube defects (NTD). In this review, the role of WIPI proteins in autophagy is discussed first, then syndromes related to these proteins are summarized.

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Consensus clinical management guideline for beta‐propeller protein‐associated neurodegeneration

Cited by 33 publications

References 31 publications

Time course of serum neuron‐specific enolase levels from infancy to early adulthood in a female patient with beta‐propeller protein‐associated neurodegeneration

Time course of serum neuron‐specific enolase levels from infancy to early adulthood in a female patient with beta‐propeller protein‐associated neurodegeneration

Cerebral Iron Deposition in Neurodegeneration

WIPI proteins: Biological functions and related syndromes

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