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]

Both disorders are characterized by progressive dementia and movement disorders, but may present earlier than PKAN. [epilepsygenetics.net]

It typically presents with gait difficulties. 2,12 Patients present pyramidal and extrapyramidal signs with marked dystonia. 2 The dystonia generally dominates the clinical picture and begins assymetrically. 12 Severe tongue protrusion dystonia can occur [demneuropsy.com.br]

• Weakness

  […] spasticity and dystonia, eye findings early in the disease, and progressive intellectual impairment and seizures later in the disease course… CoPAN CoPAN (COASY Protein-Associated Neurodegeneration) is an NBIA disorder that is characterized by spaticity and weakness [nbiacure.org]

  There is phenotypic variation: some patients may not have extrapyramidal signs and may have muscle weakness and atrophy as well as cognitive impairment or developmental delay ({1:Deschauer et al., 2012}) For a general phenotypic description and a discussion [diseaseinfosearch.org]

  Other symptoms may include: Dementia Difficulty speaking Difficulty swallowing Muscle problems such as rigidity or involuntary muscle contractions ( dystonia ) Seizures Tremor Vision loss, such as from retinitis pigmentosa Weakness Writhing movements [medlineplus.gov]

  Onset occurs in childhood to early adulthood with dystonia, spasticity, weakness, optic atrophy and neuropsychiatric changes. [nbiadisorders.org]

  Common symptoms of Neurodegeneration with Brain Iron Accumulation Type 1 include the following: Loss of side vision Progressive night blindness Muscle spasms (involuntary muscle twitches) Muscle weakness Stiffness of limbs Dystonia: Involuntary muscle [dovemed.com]

• Epilepsy

  The epilepsy phenotypes comprised myoclonic, astatic and absence seizures. Furthermore, the authors suggest that neuroimaging might be normal in childhood. [epilepsygenetics.net]

  Case report of a patient who presented with psychiatric features at age 22 years followed by progressive gait disturbance, extrapyramidal symptoms, epilepsy, and corticospinal tract involvement. [ncbi.nlm.nih.gov]

  Chief Editor Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine Selim R Benbadis, MD is a member of the [emedicine.medscape.com]

• Malnutrition

  Death typically occurs from secondary complications, including aspiration pneumonia and malnutrition. More rarely, patients have died during uncontrollable episodes of status dystonicus. [doi.org]

• Pneumonia

  She was admitted with aspiration pneumonia, and died before she could be investigated. [ncbi.nlm.nih.gov]

  Premature death usually occurs due to secondary complications such as impaired swallowing or confinement to a bed or wheelchair, which can lead to poor nutrition or aspiration pneumonia. [ninds.nih.gov]

  Death can occur secondary to dystonia, impaired swallowing, and aspiration pneumonia. TREATMENT There is currently no cure for NBIA. Treatment is symptomatic and supportive. Iron chelating medications have been attempted without significant effect. [secure.ssa.gov]

• Muscle Weakness

  There is phenotypic variation: some patients may not have extrapyramidal signs and may have muscle weakness and atrophy as well as cognitive impairment or developmental delay ({1:Deschauer et al., 2012}) For a general phenotypic description and a discussion [diseaseinfosearch.org]

  Common symptoms of Neurodegeneration with Brain Iron Accumulation Type 1 include the following: Loss of side vision Progressive night blindness Muscle spasms (involuntary muscle twitches) Muscle weakness Stiffness of limbs Dystonia: Involuntary muscle [dovemed.com]

  weakness Early spasticity sometimes followed by flaccid paresis Babinski sign Dysarthria Iron accumulation observed on brain MRI in both the globus pallidus and substantia nigra ( Figure 1B ). [ncbi.nlm.nih.gov]

  Clinically, this manifests as loss of deep tendon reflexes, muscle weakness and sometimes atrophy; electrophysiologically, as a motor neuronopathy/axonopathy [ 31, 33 – 35 ]. [doi.org]

• Muscle Cramp

  Dystonia describes involuntary muscle cramping that may force certain body parts into unusual, and sometimes painful, movements and positions. [nbiadisorders.org]

• Psychiatric Symptoms

  Case report of a patient who presented with psychiatric features at age 22 years followed by progressive gait disturbance, extrapyramidal symptoms, epilepsy, and corticospinal tract involvement. [ncbi.nlm.nih.gov]

  We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. [demneuropsy.com.br]

  Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.Pantothenate kinase-associated neurodegeneration is characterized by [icdlist.com]

  Psychiatric symptoms are more frequent in the later onset form. Retinal degeneration is common, particularly in classic PKAN. PLAN, or PLA2G6-Associated Neurodegeneration, is named for the responsible gene, PLA2G6. [nbiadisorders.org]

• Encephalopathy

  “Static encephalopathy” referred to the first phase of the disease, which resembled various neurological disorders in children, including epileptic encephalopathies. The eye of the tiger. [epilepsygenetics.net]

  Additionally, the X-linked gene WDR45 was found causative for a special subtype named static encephalopathy in childhood with neurodegeneration in adulthood (also called BPAN); however, analysis of this gene in a broader spectrum of NBIA has not been [ncbi.nlm.nih.gov]

  NBIA disorders produce a characteristic hypointensity of the basal ganglia, while other disorders, such as mitochondrial encephalopathies, organic acidurias, and abnormalities of cofactor metabolism, feature T2 hyperintensity. [sumerdoc.blogspot.com]

• Nystagmus

  Nystagmus is often present. These signs usually follow systemic signs such as difficulties in locomotion. An apraxia of eyelid opening has been noted and some patients have blepharospasm. [disorders.eyes.arizona.edu]

  Optic atrophy, nystagmus, tetraparesis, and seizures occurred similarly to infantile cases. [doi.org]

  Strabismus and nystagmus are early features of the disease. Later optic atrophy occurs in most individuals. [ncbi.nlm.nih.gov]

  […] cognitive decline Increased iron in GP and SN; “Eye of the tiger” sign very rare Fatty-acid hydroxylase-associated neurodegeneration (FAHN) FA2H autosomal recessive Onset with focal dystonia and gait impairment, ataxia, dysarthria, spastic quadriparesis, nystagmus [ojrd.biomedcentral.com]

• Paresis

  […] subtypes of PLAN: INAD, aNAD or PLA2G6-related dystonia-parkinsonism… MPAN MPAN (mitochondrial membrane protein-associated neurodegeneration) is a NBIA disorder that is characterized by gait changes in the beginning, followed by progressive spastic paresis [nbiacure.org]

  Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36 Daniel J Hampshire a, Emma Roberts a, Yanick Crow a, Jacquelyn Bond a, Ammar Mubaidin b, Abdul-Latif Wriekat b, Amir Al-Din c, C Geoffrey [doi.org]

  The onset is in the teenage years with clinical features of Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. [ncbi.nlm.nih.gov]

  Pallidopyramidal degeneration, supraneuclearupgaze paresis and dementia: Kufor- Rakeb syndrome. Acta Neurol Scand 2011;89: 347-352. Tobias B Hoak, Penelope Hogarth, Micheal C Kruer et al. Am J Hum Genet 2012 Dec 7; 91 (6): 1144-49. [journals.sbmu.ac.ir]

• Psychomotor Regression

  The disease presents with psychomotor regression (i.e., loss of previously acquired milestones) or delay, delayed walking, or gait disturbance. [ncbi.nlm.nih.gov]

  regression, hypotonia, peripheral motor neuropathy, hyperreflexia, tetraparesis, ataxia, gait abnormalities Cerebellar atrophy, abnormal iron in GP and other nuclei Atypical form: Later onset – slower progression Atypical pantothenate kinase-associated [ojrd.biomedcentral.com]

  In INAD, onset usually occurs before 2 years and psychomotor regression is the most frequent presentation. Ataxia or gait instability are also frequent in early disease. [doi.org]

• Palilalia

  Psychiatric symptoms include depression, emotional lability, impulsivity, aggressivity and tourettism with motor and verbal tics. 17 Speech disorders include dysarthria, hypophonia, spasmodic dysphonia and palilalia. [demneuropsy.com.br]

  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]

  Common speech problems are repetition of words or phrases (palilalia), rapid speech (tachylalia), and dysarthria. [rarediseases.org]

  The speech defects include palilalia (repetition of words or phrases), tachylalia/tachylogia (rapid speech of words and/or phrases), and dysarthria (poor articulation, slurring). [ncbi.nlm.nih.gov]

(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]

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. [doi.org]

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]

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]

(See Presentation and Prognosis.) [7, 8] The disease can be familial or sporadic. [emedicine.medscape.com]

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 The exact etiology of PKAN is not known. One proposed hypothesis is that abnormal peroxidation of lipofuscin to neuromelanin and deficient cysteine dioxygenase lead to abnormal iron accumulation in the brain. [emedicine.medscape.com]

Summary Epidemiology An estimated prevalence of 1-3/1,000,000 has been suggested based on observed cases in a population. [orpha.net]

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]

[…] 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]

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]

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]

Prevention of secondary complications: Adequate nutrition through swallowing evaluation, dietary assessment, gastrostomy tube feeding as needed. [sumerdoc.blogspot.com]