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Neurodegeneration with Brain Iron Accumulation

NBIA


Presentation

  • In the present review, some of the main clinical presentations, investigational findings and therapeutic results of the different NBIA disorders will be presented. Copyright 2014 Polish Neurological Society.[ncbi.nlm.nih.gov]
Rigor
  • A double-blind, placebo-controlled international multicenter clinical trial is underway to more rigorously investigate the drug’s benefit ( ).[e-jmd.org]
  • A double-blind, placebo-controlled international multicenter clinical trial is underway to more rigorously investigate the drug’s benefit ( NCT01741532 ?term deferiprone PKAN&rank 1).[ncbi.nlm.nih.gov]
Cutaneous Manifestation
  • Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegia, retinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations.[ncbi.nlm.nih.gov]
Compulsive Disorder
  • disorder, and violent outbursts. 12 – 14 Tourettism, including both verbal and motor tics, has also been observed in the early stages of atypical PKAN.[doi.org]
  • Parkinsonism (rigidity, bradykinesia, palilalia, and freezing) and prominent neuropsychiatric features, such as hyperactivity, impulsivity, obsessive-compulsive disorder, and vocal and motor tics, can be seen, as well as depression and anxiety.[ajnr.org]
Psychomotor Retardation
  • Analysis of the WDR45 gene revealed a novel heterozygous missense mutation in one female NBIA patient showing psychomotor retardation with secondary decline.[ncbi.nlm.nih.gov]
Auditory Hallucination
  • Abstract We studied a 27-year-old woman who died after a 6-year history of progressive dementia, dystonia, ataxia, apraxia, spasticity, choreoathetosis, visual and auditory hallucinations, and optic atrophy.[ncbi.nlm.nih.gov]
Overflow Incontinence
  • Treatment of bladder incontinence ideally should be guided by urodynamic studies and may need to be reassessed as the disease progresses, particularly if patients develop prominent lower motor neuron signs when urinary retention and overflow incontinence[e-jmd.org]
Urinary Retention
  • Treatment of bladder incontinence ideally should be guided by urodynamic studies and may need to be reassessed as the disease progresses, particularly if patients develop prominent lower motor neuron signs when urinary retention and overflow incontinence[e-jmd.org]
Language Development Disorder
  • The presence of hand stereotypies in some children with BPAN, along with marked abnormalities in language development, disordered sleep, and seizures may have earned them a diagnosis of “atypical Rett syndrome” before mutations in WDR45 are found.[e-jmd.org]
Shuffling Gait
  • One patient experienced gradual onset of shuffling gait, rigidity, bradykinesia, and increasing postural instability at age 85 years. He died a few weeks after developing acute hemiballismus at age 90 years.[ncbi.nlm.nih.gov]
Motor Disturbances
  • Additional mild ocular motor disturbances included low gain pursuit (2), hypermetric saccades (1), low gain optokinetic (2) and caloric and rotatory responses (3).[ncbi.nlm.nih.gov]
Spastic Quadriplegia
  • Affected children are profoundly hypotonic and later develop a progressive spastic quadriplegia with pyramidal dysfunction. Optic atrophy leads to loss of visual acuity and ultimate blindness. Dementia is usually relentlessly progressive.[ajnr.org]

Workup

  • Mood lability, impulsivity, non-specific behavioral changes, and obsessive-compulsive features may be early signs and may be attributed to typical changes of adolescence until other neurologic signs appear, prompting further workup.[e-jmd.org]
  • (See Presentation and Workup.) [4, 5, 6] PKAN is relentlessly progressive. The clinical course is characterized by progressive dementia, spasticity, rigidity, dystonia, and choreoathetosis.[emedicine.medscape.com]

Treatment

  • The first results of treatments with modern chelating drugs are also being published.[ncbi.nlm.nih.gov]
  • Management and treatment At this time most treatments for NBIA are palliative. Research is currently underway to identify additional NBIA genes and improve treatment possibilities by characterizing the underlying causes of these disorders.[orpha.net]

Prognosis

  • For those with atypical, late-onset NBIA, many are diagnosed as adults and live well into adulthood. x Prognosis NBIA is a progressive condition.[ninds.nih.gov]
  • […] spasms, parkinsonism neuropsychiatric optic atrophy retinal degeneration Radiographic features will vary among the various entities, but can broadly be thought of as 3 : basal ganglia signal abnormalities cerebellar and cerebral atrophy Treatment and prognosis[radiopaedia.org]
  • Her disease has a poor prognosis and she was told she likely would have 5-10 good years ahead of her before the iron accumulation becomes too great. That was 5 years ago.[youcaring.com]
  • (See Presentation and Prognosis.) [7, 8] The disease can be familial or sporadic.[emedicine.medscape.com]

Etiology

  • This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.[ncbi.nlm.nih.gov]
  • Etiology Classic and atypical PKAN are caused by mutations in the PANK2 gene (20p13-p12.3), infantile and atypical neuroaxonal dystrophy are caused by mutation in the PLA2G6 gene (22q13.1), aceruloplasminemia is caused by mutation of the ceruloplasmin[orpha.net]
  • (Etiology) Neurodegeneration with Brain Iron Accumulation Type 1 is an autosomal recessive disorder with the following characteristics: Around 50% of individuals with NBIA1 have mutation in the PKAN2 gene This gene is responsible for assisting the metabolism[dovemed.com]
  • This report not only illustrates that WES is a powerful tool to elucidate the etiology of rare genetic diseases, but also identifies unique neuroimaging and metabolic findings that may be key features for an early diagnosis of CoPAN.[doi.org]

Epidemiology

  • Summary Epidemiology An estimated prevalence of 1-3/1,000,000 has been suggested based on observed cases in a population.[orpha.net]
  • […] dystrophy (NAD) aceruloplasminaemia COASY protein-associated neurodegeneration (COPAN) fatty acid hydroxylase-associated neurodegeneration (FAHN) Kufor-Rakeb syndrome neuroferritinopathy Woodhouse-Sakati syndrome No single demographic is affected, and epidemiology[radiopaedia.org]
  • To collect epidemiological data about NBIA in Hungary. BACKGROUND:Neurodegeneration with Brain Iron Accumulation(NBIA) is a group of disorders characterized by progressive movement disordres and iron accumulation in the basal ganglia.[neurology.org]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiologically, many of the NBIA syndromes map into related biochemical pathways and gene networks including mitochondrial pathways, lipid metabolism, and autophagy.[ncbi.nlm.nih.gov]
  • This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system.[scienceopen.com]

Prevention

  • Current medical options for these disorders remain largely unsatisfactory and do not prevent the disease from progressing to a severe and disabling state.[ncbi.nlm.nih.gov]
  • Neurodegeneration with Brain Iron Accumulation Type 1 have mutation in PKAN2 gene Though not widely available, genetic testing for mutated PKAN2 gene can confirm Neurodegeneration with Brain Iron Accumulation Type 1 There is no definitive treatment and prevention[dovemed.com]
  • Considering that valid therapeutic alternatives of proven preventive and/or curative efficacy in these neurodegenerative diseases do not exist today, the use of lipophilic iron chelators must be considered as a possible therapeutic strategy worthy of[clinicaltrials.gov]
  • There is no known way to prevent it. Hallervorden-Spatz disease; Pantothenate kinase-associated neurodegeneration; PKAN; NBIA Gregory A, Hayflick S. Neurodegeneration with brain iron accumulation disorders overview.[medlineplus.gov]

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