{"orpha":35069,"name":"PLA2G6-related neurodegeneration, infantile-onset","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["INAD","Infantile neuroaxonal dystrophy","Infantile PLAN","Infantile phospholipase A2-associated neurodegeneration","Seitelberger disease","PLA2G6-associated neurodegeneration, infantile-onset"],"definition":"A rare neurodegeneration with brain iron accumulation (NBIA) disorder characterized by global developmental delay and eventual regression, increasing neurological involvement with symmetrical spastic tetraplegia, loss of cognitive and bulbar function, seizures and optic atrophy. The infantile form of PLAN, which has onset before three years of age, is most common relative to juvenile-onset and adult-onset forms, and individuals may present with symptoms anywhere along a continuum.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-35069/","orphanet_url":"https://www.orpha.net/en/disease/detail/35069","names":{"fr":{"name":"Neurodégénérescence associée à PLA2G6 à début infantile","synonyms":["DNAI","Maladie de Seitelberger","Dystrophie neuroaxonale infantile","Neurodégénérescence associée à la phospholipase A2 infantile"],"definition":"Neurodégénérescence rare avec surcharge cérébrale en fer (DNAI), caractérisée par un retard global de développement pouvant évoluer vers une régression, une atteinte neurologique progressive se traduisant par une tétraplégie spastique symétrique, une perte des fonctions cognitives et bulbaires, des crises épileptiques et une atrophie optique. La forme infantile de la DNA, se manifestant avant l'âge de trois ans, est la plus courante par rapport aux formes juvéniles et adultes, et les symptômes peuvent se manifester à n'importe quel stade de ce continuum."},"de":{"name":"PLA2G6-assoziierte Neurodegeneration, infantile Form","synonyms":["INAD","Infantile PLAN","Infantile neuroaxonale Dystrophie","Phospholipase A2-assoziierte Neurodegeneration mit Beginn im Kindesalter","Seitelberger Krankheit"],"definition":"Die Infantile neuroaxonale Dystrophie/atypische neuroaxonale Dystrophie (INAD/atypische NAD) ist eine Form der Neurodegeneration mit Eisenakkumulation im Gehirn (NBIA; siehe diesen Begriff), die durch psychomotorische Regression und zunehmende neurologische Probleme gekennzeichnet ist: Symmetrische Pyramidenbahnzeichen; ausgeprägte Hypotonie des Stamms, die bis zu spastischer Tetraplegie fortschreitet; Sehstörungen und Demenz. INAD kann klassisch oder atypisch sein und Patienten können das gesamte Spektrum der Symptome innerhalb dieses Kontinuums aufweisen."},"es":{"name":"Neurodegeneración asociada al gen PLA2G6 de inicio en la lactancia","synonyms":["Enfermedad de Seitelberger","INAD","Distrofia neuroaxonal infantil","Neurodegeneración asociada a fosfolipasa A2 en la lactancia","PLAN del lactante"],"definition":"La distrofia neuroaxonal infantil / distrofia neuroaxonal atípica (INAD / NAD atípica) es un tipo de neurodegeneración con acumulación cerebral de hierro (NBIA, véase este término) que se caracteriza por retraso psicomotor y regresión, afectación neurológica progresiva y simétrica del tracto piramidal y tetraplejía espástica. La INAD puede ser clásica o atípica y los pacientes pueden presentar síntomas en un espectro contínuo que va de un tipo al otro."},"it":{"name":"Neurodegenerazione ad esordio infantile correlata a PLA2G6","synonyms":["INAD","PLAN infantile","Malattia di Seitelberger","Distrofia neuroassonale infantile","Neurodegenerazione ad esordio infantile associata a PLA2G6","Neurodegenerazione infantile associata alla fosfolipasi A2"]},"nl":{"name":"PLA2G6-gerelateerde neurodegeneratie, infantiele aanvang","synonyms":["INAD","Infantiele neuroaxonale dystrofie","Neurodegeneratie geassocieerd met fosfolipase A2 bij zuigeling","Ziekte van Seitelberger","PLA2G6-eassocieerde neurodegeneratie beginnend op zuigelingenleeftijd","PLAN bij zuigeling"],"definition":"Infantiele neuroaxonale dystrofie/atypische neuroaxonale dystrofie (INAD/atypische NAD) is een type van neurodegeneratie met accumulatie van ijzer in hersenen (NBIA), gekenmerkt door psychomotorische achterstand en regressie, toenemende neurologische betrokkenheid met symmetrische verschijnselen van piramidebaan en spastische tetraplegie. INAD kan klassiek of atypisch zijn, en patiënten presenteren zich met symptomen langsheen een continuüm tussen deze twee."},"pt":{"name":"Distrofia neuroaxonal do lactente","synonyms":["Doença de Seitelberger","INAD"]},"pl":{"name":"Dziecięca dystrofia neuroaksonalna","synonyms":["Choroba Seitelbergera","INAD","INAD1","Neurodegeneracja zwiazana z fosfolipazą A2","plAN"]},"cs":{"name":"Infantilní neuroaxonální dystrofie","synonyms":["INAD","INAD1","PLAN","Neurodegenerace spojená s fosfolipázou A2","Seitelbergerova nemoc"]},"uk":{"name":"Дитяча нейроаксональна дистрофія","synonyms":["ІНАД","INAD1","Фосфоліпаза А2-асоційована нейродегенерація","PLAN","Хвороба Зайтельбергера"],"definition":"Infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy (INAD/atypical NAD) is a type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two."},"zh":{"name":"婴儿神经轴索营养不良","synonyms":["非钙依赖型磷脂酶A2相关性神经退行性病变"]},"tr":{"name":"İnfantil nöroaksonal distrofi","synonyms":["INAD","PLAN","INAD1","Seitelberger hastalığı","Fosfolipaz A2 ile ilişkili nörodejenerasyon"]}},"xrefs":[{"source":"OMIM","code":"256600","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"610217","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G31.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C64.10","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"730637493"},{"source":"UMLS","code":"C0270724","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3957","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10088200","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":2174,"name":"Hunter-Carpenter-McDonald syndrome","status":"inactive"}],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":98497,"name":"Genetic peripheral neuropathy","classifications":[156,181]},{"orpha":329303,"name":"PLA2G6-related neurodegeneration","classifications":[150,156,181]}],"children":[],"genes":[{"symbol":"PLA2G6","name":"phospholipase A2 group VI","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"9039","ensembl":"ENSG00000184381","omim":"603604","loci":["22q13.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":150.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-01-25","source":"27884548[PMID]_ 29409688[PMID]_20301718[PMID]","terms":[{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002361","label":"Psychomotor deterioration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003134","label":"Abnormality of peripheral nerve conduction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000649","label":"Abnormality of visual evoked potentials","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002483","label":"Bulbar signs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012698","label":"Cerebellar gliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003405","label":"Diffuse axonal swelling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003444","label":"EMG: chronic denervation signs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002454","label":"Eye of the tiger anomaly of globus pallidus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025435","label":"Increased circulating lactate dehydrogenase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012675","label":"Iron accumulation in brain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001268","label":"Mental deterioration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002191","label":"Progressive spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007141","label":"Sensorimotor neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001285","label":"Spastic tetraparesis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002317","label":"Unsteady gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012332","label":"Abnormal autonomic nervous system physiology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011951","label":"Aspiration pneumonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000618","label":"Blindness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002019","label":"Constipation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000752","label":"Hyperactivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100710","label":"Impulsivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012043","label":"Pendular nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000736","label":"Short attention span","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005968","label":"Temperature instability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005949","label":"Apneic episodes in infancy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0030842","label":"Choking episodes","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0010545","label":"Downbeat nystagmus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0025331","label":"Upgaze palsy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0031358","label":"Vegetative state","frequency":"Very rare (<4-1%)","criteria":null}]}}