Neurodegeneration with Brain Iron Accumulation 5 (NBIA5)

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Disease Ontology 12 DOID:0110739 OMIM® 57 300894 OMIM Phenotypic Series 57 PS234200 MeSH 44 D001480 D019150 D019189 ICD10 32 G23.0

ICD10 via Orphanet 33 G23.0 Orphanet 58 ORPHA329284 MedGen 41 C3550973 CN169527 SNOMED-CT via HPO 68 103252009 128613002 16046003 224958001 228156007 246545002 247578003 248004009 26079004 278849000 312444006 313307000 32798002 399317006 418143002 52448006 52522001 53888004 61372001 76976005 84757009 91138005 91175000 95646004 more UMLS 70 C3550973

MedlinePlus Genetics : ⁴³ Beta-propeller protein-associated neurodegeneration (BPAN) is a disorder that damages the nervous system and is progressive, which means that it gradually gets worse. Affected individuals develop a buildup of iron in the brain that can be seen with medical imaging. For this reason, BPAN is classified as a type of disorder called neurodegeneration with brain iron accumulation (NBIA), although the iron accumulation may not occur until late in the disease.Many people with BPAN have recurrent seizures (epilepsy) beginning in infancy or early childhood. Several different types of seizures can occur in this disorder, even in the same individual. Often the first type to occur are febrile seizures, which are triggered by a high fever. Affected individuals can also experience generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Other seizure types that can occur in this disorder include short lapses in awareness that can have the appearance of staring spells or daydreaming (absence seizures, also called petit mal seizures), sudden episodes of weak muscle tone (atonic seizures), involuntary muscle twitches (myoclonic seizures), or more pronounced movements called epileptic spasms. Some individuals have seizure patterns that resemble those in epileptic syndromes, such as West syndrome or Lennox-Gastaut syndrome.Children with BPAN also have intellectual disability, delayed development including significant problems with vocabulary and producing speech (expressive language), and difficulty coordinating movements (ataxia). Ataxia can affect the ability to walk and perform fine motor skills such as using utensils. Affected individuals can have behavioral changes that are often compared to features of a disorder called Rett syndrome. These features include repeated hand wringing or clasping (stereotypic hand movements); teeth grinding (bruxism); sleep disturbances; and problems with communication and social interaction characteristic of autism spectrum disorder.In late adolescence or early adulthood, individuals with BPAN may begin to experience a gradual loss of intellectual functioning (cognitive decline) that can lead to a severe loss of thinking and reasoning abilities (dementia). Worsening problems with movement also occur, including dystonia and parkinsonism. Dystonia is a condition characterized by involuntary, sustained muscle contractions. In BPAN, the dystonia often starts in the arms. Parkinsonism can include unusually slow movement (bradykinesia), rigidity, tremors, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls.The lifespan of people with BPAN varies. With proper management of their signs and symptoms, affected individuals can live into middle age. Death may result from complications of dementia or movement problems, such as injuries from falls or swallowing difficulties (dysphagia) that can lead to a bacterial lung infection called aspiration pneumonia.

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation 5, also known as beta-propeller protein-associated neurodegeneration, is related to alcohol-related neurodevelopmental disorder and movement disease, and has symptoms including tremor, abnormality of extrapyramidal motor function and bradykinesia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 5 is WDR45 (WD Repeat Domain 45), and among its related pathways/superpathways are Biosynthesis of cofactors and Spinocerebellar ataxia. Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are intellectual disability and sleep disturbance

Disease Ontology : ¹² A neurodegeneration with brain iron accumulation that has material basis in X-linked dominant inheritance of mutation in the WDR45 gene on chromosome Xp11.23.

GARD : ²⁰ Beta-propeller protein -associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a hereditary neurologic disorder. It is part of the group of disorders known as neurodegeneration with brain iron accumulation. This disorder presents with global developmental delay in childhood which becomes progressive in early adulthood. Symptoms include dystonia (a movement disorder resulting in muscular spasms, twisting and repetitive movements) spasticity, parkinsonism (slurred or slow speech, stiffness of the muscles, slow movement, and visible tremors), and cognitive decline. BPAN is caused by mutations in the WDR45 gene. It is inherited in a dominant X-linked manner. Treatment is aimed at addressing the symptoms found in each individual.

OMIM® : ⁵⁷ NBIA5, sometimes referred to as 'static encephalopathy of childhood with neurodegeneration in adulthood (SENDA),' is an X-linked neurodegenerative disorder characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability. Brain MRI shows iron accumulation in the globus pallidus and substantia nigra. A characteristic finding is T1-weighted hyperintensity surrounding a central band of hypointensity in the substantia nigra. Cerebral and cerebellar atrophy are also observed (summary by Haack et al., 2012 and Saitsu et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200). (300894) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : ⁷² Neurodegeneration with brain iron accumulation 5: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA5 is characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability.

GeneReviews: NBK424403

Clinical features from OMIM®:

300894 (Updated 20-May-2021)

Search Clinical Trials , NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation 5

Search GEO for disease gene expression data for Neurodegeneration with Brain Iron Accumulation 5.