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]

• Severe Pain

  Other conditions were excluded as follows: Hereditary insensitivity to pain otherwise called human pin cushions are symptomatic from birth not appreciating any pain resulting in severe mutilation of lips, tongue, auto amputation of limbs and death within [e-ijd.org]

  When After start walking, a sudden severe pain pop out in both lower limbs and by standing and short resting it get resolved fast. Neurological examination revealed marked diffuse rigidity (both pyramidal and extra pyramidal). Tone was increased. [ncbi.nlm.nih.gov]

• Difficulty Walking

  All had progressive cognitive and motor regression first noted between 9 months and 6 years of age that typically first manifested as difficulty walking (ataxia). Ophthalmic examination was sometimes limited by cognitive ability. [ncbi.nlm.nih.gov]

  The disorder is caused by a mutation on a gene located on the X chromosome, which is why Madison, now 3, can’t speak, has difficulty walking, and lacks other motor skills. [dailynews.com]

• Widely Spaced Teeth

  Cornelia de Lange syndrome manifests as intrauterine growth retardation, low birth weight, mental retardation, microcephaly, facial dysmorphism in the form of arched eye brows which meet in the middle, low set ears, small upturned nose and widely spaced [e-ijd.org]

• Ulcer

  Examination of her lips showed ulcerated, swollen lower and upper lips [Figure 1]. Several parts of the lower lips were missing. The ulcers were showing yellowish slough with areas of bleed. Her angle of the mouth showed ulceration and pigmentation. [e-ijd.org]

• Torticollis

  RESULTS:The clinical symptoms varied from mild parkinsonism over isolated torticollis to severe dystonia. In 16 of 22 patients with NBIA we could identify the genetic background of the disease. [neurology.org]

  Specific forms of dystonia that may occur in association with NBIA include blepharospasm and torticollis. [nbiadisorders.org]

  Specific forms of dystonia that may occur in association with PKAN include blepharospasm and torticollis. [rarediseases.org]

• Hip Dislocation

  Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation). [ncbi.nlm.nih.gov]

• Arthritis

  Lesch-Nyhan syndrome is an X-linked disorder, affects males which presents with athetosis, dystonia, chorea, and elevated uric acid with gouty arthritis. The above phenotypic characters clearly differentiate NBIA from these conditions. [e-ijd.org]

• Kayser-Fleischer Ring

  […] abnormalities w/cognitive/psychiatric features More prominent extrapyramidal signs Pallidal iron Neurodegenerative mineral deposition disorder Wilson disease ATP7B AR Gait disturbance Spasticity Dystonia T 2 -weighted hypointensity of globus pallidus Kayser-Fleischer [ncbi.nlm.nih.gov]

• Low Set Ears

  Cornelia de Lange syndrome manifests as intrauterine growth retardation, low birth weight, mental retardation, microcephaly, facial dysmorphism in the form of arched eye brows which meet in the middle, low set ears, small upturned nose and widely spaced [e-ijd.org]

• Self-Mutilation

  Self-mutilation in neurodegeneration with brain iron accumulation. Indian J Dermatol 2015;60:290-2 How to cite this URL: Chandra SR, Raj P, Issac TG. Self-mutilation in neurodegeneration with brain iron accumulation. [e-ijd.org]

• Self-Mutilation

  Self-mutilation in neurodegeneration with brain iron accumulation. Indian J Dermatol 2015;60:290-2 How to cite this URL: Chandra SR, Raj P, Issac TG. Self-mutilation in neurodegeneration with brain iron accumulation. [e-ijd.org]

• Chorea

  […] scp=84930147873&partnerID=8YFLogxK U2 - 10.1007/978-1-4471-6455-5_10 DO - 10.1007/978-1-4471-6455-5_10 M3 - Chapter SN - 9781447164555 SN - 1447164547 SN - 9781447164548 SP - 171 EP - 198 BT - Chorea : Causes and Management PB - Springer-Verlag London [moh-it.pure.elsevier.com]

  […] syndrome Woodhouse-Sakati syndrome is an NBIA disorder characterized by both neurologic and endocrine symptoms… Neuroferritinopathy Neuroferritinopathy is a NBIA disorder characterized by symptoms that are similar to Huntington disease with adult-onset chorea [nbiacure.org]

  […] or dystonia, orofacial action dystonia, cognitive decline Abnormal iron and later cystic changes in the basal ganglia Aceruloplasminemia CP autosomal recessive Diabetes mellitus, retinal degeneration, blepharospasm, facial and neck dystonia, chorea, [ojrd.biomedcentral.com]

  Lesch-Nyhan syndrome is an X-linked disorder, affects males which presents with athetosis, dystonia, chorea, and elevated uric acid with gouty arthritis. The above phenotypic characters clearly differentiate NBIA from these conditions. [e-ijd.org]

  Aceruloplasminemia (ACP) • Loss of function mutations in the CP gene, encoding the protein ceruloplasmin • Present in mid-adulthood • Blepharospasm, chorea, craniofacial dyskinesias, ataxia, and retinal degeneration • MRI reveals iron deposition in CN [slideshare.net]

• Peripheral Neuropathy

  Peripheral neuropathy may be seen in a subset of patients with WSS. Intellectual impairment is typical and may be progressive. [ajnr.org]

  Neuroacanthocytosis presents with progressive peripheral neuropathy, ataxia, retinitis pigmentosa, oromandibular dyskinesias and acanthocytes in the peripheral smear. [e-ijd.org]

  neuropathy Spastic paraplegia 15 ZFYVE26 AR Arylsulfatase A deficiency (juvenile metachromatic leukodystrophy) ARSA AR Early childhood motor regression Spasticity Dysarthria Behavior & cognitive ability decline first More frequent peripheral neuropathy [ncbi.nlm.nih.gov]

  Neuroaxonal dystrophy (NAD) • Mutations in the gene encoding calcium- independent phospholipase A2 (PLA2G6) • Progressive spasticity, ataxia, and dystonia • Optic atrophy, peripheral neuropathy, and cognitive impairment • MRI reveals – Iron deposition [slideshare.net]

• Extrapyramidal 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]

  Patients with NBIA suffer from a variety of neurological symptoms and signs including 3 : extrapyramidal symptoms dystonia, muscular rigidity, spasms, parkinsonism neuropsychiatric optic atrophy retinal degeneration Radiographic features will vary among [radiopaedia.org]

  DESIGN/METHODS:We examined 22 patients with extrapyramidal symptoms and brain iron accumulation (10 male, 12 female, mean age 35.1 years). The entire coding regions of the genes PANK2, PLA2G6, MPAN and CP were sequenced. [neurology.org]

  Case Report: 32 yr old lady of non consanguineous parents with two decades history of seizures, altered behavior (no definite extrapyramidal symptoms), shows on MRI, symmetrical regions of relative low signal foci on all sequences including SWI ,in basal [sumerdoc.blogspot.com]

• Apraxia

  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]

  This 10-year-old child presented with progressive generalized dystonia with opisthotonus, oromandibular dyskinesias, apraxia for swallowing and self-mutilating behavior. [e-ijd.org]

  An apraxia of eyelid opening has been noted and some patients have blepharospasm. Systemic Features: This is a progressive disorder of the basal ganglia with prominent symptoms of extrapyramidal dysfunction. [disorders.eyes.arizona.edu]

• Opisthotonus

  In evaluating patients with NBIAs in our centers, we have observed that action-induced dystonic opisthotonus is a common and characteristic feature of NBIAs. [ncbi.nlm.nih.gov]

  This 10-year-old child presented with progressive generalized dystonia with opisthotonus, oromandibular dyskinesias, apraxia for swallowing and self-mutilating behavior. [e-ijd.org]

  Dystonic Opisthotonus: A "Red Flag" for Neurodegeneration With Brain Iron Accumulation Syndromes? Mov Disord 2013;28:1325-1329. 15. Egan RA, Weleber RG, Hogarth P, et al. [demneuropsy.com.br]

(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]

• Acanthocytes

  Blood smear showed a large number of acanthocytes (Figure 1). Figure 1. Blood smear shows numerous acanthocytes. [demneuropsy.com.br]

  Neuroacanthocytosis presents with progressive peripheral neuropathy, ataxia, retinitis pigmentosa, oromandibular dyskinesias and acanthocytes in the peripheral smear. [e-ijd.org]

  Since the discovery of PANK2, it has been established that the association of hyperprebetalipoproteinaemia, acanthocytes, and retinitis pigmentosa (HARP) is within the PKAN spectrum. 9 Acanthocytes may be observed in other cases of PKAN as well. 10 11 [doi.org]

  Acanthocytes have been reported in a subset of individuals with PKAN [ Schiessl-Weyer et al 2015 ]. [ncbi.nlm.nih.gov]

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]