{"orpha":135,"name":"CACH syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Childhood ataxia with diffuse central nervous system hypomyelination","Leukoencephalopathy with vanishing white matter","Myelinosis centralis diffusa"],"definition":"A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes ``foamy'' aspect.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-135/","orphanet_url":"https://www.orpha.net/en/disease/detail/135","names":{"fr":{"name":"Syndrome CACH","synonyms":["Ataxie infantile avec hypomyélinisation diffuse du système nerveux central","Leucoencéphalopathie avec perte de substance blanche","Myélinolyse centrale diffuse"],"definition":"Une nouvelle entité clinico-IRM de leucodystrophie a été individualisée sous les termes de syndrome CACH (Childhood Ataxia with Central nervous system Hypomyelination) puis VWM (Vanishing White Matter). Elle associe classiquement (1) un début entre l'âge de 2 et 5 ans par un syndrome cérébello-spastique, souvent révélé ou exacerbé par un traumatisme crânien bénin ou une infection virale banale, aboutissant au décès en moyenne après 5 à 10 ans d'évolution, (2) une atteinte diffuse de la substance blanche sus-tentorielle en IRM, d'aspect cavitaire, (3) un mode de transmission récessif autosomique, (4) un aspect neuropathologique de leucodystrophie orthochromatique cavitaire avec augmentation du nombre des oligodendrocytes prenant parfois un aspect spumeux."},"de":{"name":"CACH-Syndrom","synonyms":["Infantile Ataxie mit diffuser Hypomyelinisierung des ZNS","Leukoenzephalopathie mit Verlust der weissen Hirnsubstanz","Myelinosis centralis diffusa"],"definition":"Eine neue Leukenzephalopathie, das CACH-Syndrom (<u>C</u>hildhood <u>A</u>taxia with <u>C</u>entral nervous system <u>H</u>ypomyelination) oder VWM (<u>V</u>anishing <u>W</u>hite <u>M</u>atter) wurde aufgrund klinischer und MRI-Kriterien definiert. Klassische Symptome sind: (1) Zerebellär-spastisches Syndrom mit Beginn im Alter von 2 bis 5 Jahren. Die Symptome exazerbieren mit Fieberschüben oder Schädeltrauma. Tod 5-10 Jahre nach Beginn der Symptome; (2) In der zerebralen MRI diffuse Beteiligung der weißen Substanz mit CSF-ähnlicher Signalintensität (Kavitation); (3) Autosomal-rezessive Vererbung; (4) Neuropathologische Befunde einer hohlraum-bildenden orthochromatischen Leukodystrophie mit vermehrter Zahl von Oligodendrozyten, manchmal mit 'schaumigem' Aspekt."},"es":{"name":"Síndrome CACH","synonyms":["Ataxia infantil con hipomielinización del sistema nervioso central","Leucoencefalopatía con desaparición de la sustancia blanca","Mielinosis central difusa"],"definition":"Se trata de una leucoencefalopatía identificada en base a criterios clínicos y de resonancia magnética. Clásicamente, esta enfermedad se caracteriza por: (1) un inicio entre los 2 y 5 años de edad, con un síndrome cerebelo-espástico exacerbado por episodios de fiebre o traumatismo craneoencefálico que lleva a la muerte después de 5 a 10 años de evolución de la enfermedad, (2) un compromiso difuso de la sustancia blanca en la RM cerebral con una intensidad de señal similar a la del LCR (cavitación), (3) un modo de herencia autosómico recesivo, (4) hallazgos neuropatológicos consistentes con una leucodistrofia ortocromática cavitante, con aumento del número de oligodendrocitos con aspecto \"espumoso\" en algunos casos."},"it":{"name":"Sindrome CACH","synonyms":["Atassia infantile con ipomielinizzazione diffusa del sistema nervoso centrale","Leucoencefalopatia con perdita della sostanza bianca","Mielinolisi centrale diffusa"]},"nl":{"name":"CACH-syndroom","synonyms":["Ataxie op kinderleeftijd met diffuse hypomyelinisatie van centraal zenuwstelsel","Leuko-encefalopathie met verdwijnende witte stof","Myelinosis centralis diffusa"],"definition":"CACH-syndroom (ataxie in de kindertijd met diffuse hypomyelinisatie van centraal zenuwstelsel) of VWM (verdwijnende witte stof) is een leuko-encefalopathie, geïdentificeerd op basis van criteria van klinisch onderzoek en MRI. Doorgaans wordt de ziekte gekenmerkt door (1) aanvangsleeftijd tussen 2 en 5 jaar, met cerebello-spastisch syndroom verergerd door episodes van koorts of hoofdtrauma en resulterend in sterfte na 5 tot 10 jaar van evolutie van de ziekte, (2) diffuse betrokkenheid van witte stof bij cerebrale MRI met CSV-achtige signaalintensiteit (cavitatie), (3) autosomaal recessieve overerving, (4) neuropathologische bevindingen consistent met caviterende orthochromatische leukodystrofie met verhoogd aantal oligodendrocyten die soms een 'schuimig' voorkomen hebben."},"pt":{"name":"Síndrome CACH","synonyms":["Ataxia infantil com hipomielinização difusa do SNC","Leucoencefalopatia com desaparecimento de substância branca","Mielinose central difusa"]},"pl":{"name":"Zespół CACH","synonyms":["Dziecięca ataksja z rozlaną hipomielinizacją centralnego układu nerwowego","Leukoencefalopatia z zanikającą istotą białą","Myelinosis centralis diffusa"]},"cs":{"name":"CACH syndrom","synonyms":["Leukoencefalopatie s mizející bílou hmotou","Myelinosis centralis diffusa","Dětská ataxie s difuzní hypomyelinizací centrálního nervového systému"]},"uk":{"name":"CACH-синдром","synonyms":["Дитяча атаксія з дифузною гіпомієлінізацією центральної нервової системи","Лейкоенцефалопатія зі зникненням білої речовини","Центральний дифузний мієліноз"],"definition":"A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes ``foamy'' aspect."},"zh":{"name":"CACH综合征","synonyms":["弥漫性中枢神经系统髓鞘形成减少伴儿童期共济失调"]},"tr":{"name":"CACH sendromu","synonyms":["Myelinozis sentralis diffusa","Kaybolan beyaz cevher ile seyreden lökoensefalopati","Yaygın merkezi sinir sistemi hipomiyelinizasyon ile seyreden çocukluk çağı ataksisi"]}},"xrefs":[{"source":"OMIM","code":"603896","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"615889","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620312","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620313","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620314","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620315","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8A44.3","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1574637700"},{"source":"MONDO","code":"0800448","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1858991","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"231","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]}],"children":[{"orpha":157713,"name":"Congenital or early infantile CACH syndrome","type":"Clinical subtype"},{"orpha":99854,"name":"Cree leukoencephalopathy","type":"Clinical subtype"},{"orpha":157719,"name":"Juvenile or adult CACH syndrome","type":"Clinical subtype"},{"orpha":157716,"name":"Late infantile CACH syndrome","type":"Clinical subtype"},{"orpha":99853,"name":"Ovarioleukodystrophy","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"AARS2","name":"alanyl-tRNA synthetase 2, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24808023[PMID]","hgnc":"21022","ensembl":"ENSG00000124608","omim":"612035","loci":["6p21.1"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B1","name":"eukaryotic translation initiation factor 2B subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3257","ensembl":"ENSG00000111361","omim":"606686","loci":["12q24.31"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B1","name":"eukaryotic translation initiation factor 2B subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3257","ensembl":"ENSG00000111361","omim":"606686","loci":["12q24.31"],"via":{"orpha":99854,"name":"Cree leukoencephalopathy"}},{"symbol":"EIF2B1","name":"eukaryotic translation initiation factor 2B subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3257","ensembl":"ENSG00000111361","omim":"606686","loci":["12q24.31"],"via":{"orpha":157713,"name":"Congenital or early infantile CACH syndrome"}},{"symbol":"EIF2B1","name":"eukaryotic translation initiation factor 2B subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3257","ensembl":"ENSG00000111361","omim":"606686","loci":["12q24.31"],"via":{"orpha":157716,"name":"Late infantile CACH syndrome"}},{"symbol":"EIF2B1","name":"eukaryotic translation initiation factor 2B subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3257","ensembl":"ENSG00000111361","omim":"606686","loci":["12q24.31"],"via":{"orpha":157719,"name":"Juvenile or adult CACH syndrome"}},{"symbol":"EIF2B2","name":"eukaryotic translation initiation factor 2B subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3258","ensembl":"ENSG00000119718","omim":"606454","loci":["14q24.3"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B2","name":"eukaryotic translation initiation factor 2B subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3258","ensembl":"ENSG00000119718","omim":"606454","loci":["14q24.3"],"via":{"orpha":99854,"name":"Cree leukoencephalopathy"}},{"symbol":"EIF2B2","name":"eukaryotic translation initiation factor 2B subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3258","ensembl":"ENSG00000119718","omim":"606454","loci":["14q24.3"],"via":{"orpha":157713,"name":"Congenital or early infantile CACH syndrome"}},{"symbol":"EIF2B2","name":"eukaryotic translation initiation factor 2B subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3258","ensembl":"ENSG00000119718","omim":"606454","loci":["14q24.3"],"via":{"orpha":157716,"name":"Late infantile CACH syndrome"}},{"symbol":"EIF2B2","name":"eukaryotic translation initiation factor 2B subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3258","ensembl":"ENSG00000119718","omim":"606454","loci":["14q24.3"],"via":{"orpha":157719,"name":"Juvenile or adult CACH syndrome"}},{"symbol":"EIF2B3","name":"eukaryotic translation initiation factor 2B subunit gamma","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3259","ensembl":"ENSG00000070785","omim":"606273","loci":["1p34.1"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B3","name":"eukaryotic translation initiation factor 2B subunit gamma","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3259","ensembl":"ENSG00000070785","omim":"606273","loci":["1p34.1"],"via":{"orpha":99854,"name":"Cree leukoencephalopathy"}},{"symbol":"EIF2B3","name":"eukaryotic translation initiation factor 2B subunit gamma","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3259","ensembl":"ENSG00000070785","omim":"606273","loci":["1p34.1"],"via":{"orpha":157713,"name":"Congenital or early infantile CACH syndrome"}},{"symbol":"EIF2B3","name":"eukaryotic translation initiation factor 2B subunit gamma","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3259","ensembl":"ENSG00000070785","omim":"606273","loci":["1p34.1"],"via":{"orpha":157716,"name":"Late infantile CACH syndrome"}},{"symbol":"EIF2B3","name":"eukaryotic translation initiation factor 2B subunit gamma","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3259","ensembl":"ENSG00000070785","omim":"606273","loci":["1p34.1"],"via":{"orpha":157719,"name":"Juvenile or adult CACH syndrome"}},{"symbol":"EIF2B4","name":"eukaryotic translation initiation factor 2B subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3260","ensembl":"ENSG00000115211","omim":"606687","loci":["2p23.3"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B4","name":"eukaryotic translation initiation factor 2B subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3260","ensembl":"ENSG00000115211","omim":"606687","loci":["2p23.3"],"via":{"orpha":99854,"name":"Cree leukoencephalopathy"}},{"symbol":"EIF2B4","name":"eukaryotic translation initiation factor 2B subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3260","ensembl":"ENSG00000115211","omim":"606687","loci":["2p23.3"],"via":{"orpha":157713,"name":"Congenital or early infantile CACH syndrome"}},{"symbol":"EIF2B4","name":"eukaryotic translation initiation factor 2B subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3260","ensembl":"ENSG00000115211","omim":"606687","loci":["2p23.3"],"via":{"orpha":157716,"name":"Late infantile CACH syndrome"}},{"symbol":"EIF2B4","name":"eukaryotic translation initiation factor 2B subunit delta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3260","ensembl":"ENSG00000115211","omim":"606687","loci":["2p23.3"],"via":{"orpha":157719,"name":"Juvenile or adult CACH syndrome"}},{"symbol":"EIF2B5","name":"eukaryotic translation initiation factor 2B subunit epsilon","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3261","ensembl":"ENSG00000145191","omim":"603945","loci":["3q27.1"],"via":{"orpha":99853,"name":"Ovarioleukodystrophy"}},{"symbol":"EIF2B5","name":"eukaryotic translation initiation factor 2B subunit epsilon","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]_15136673[PMID]","hgnc":"3261","ensembl":"ENSG00000145191","omim":"603945","loci":["3q27.1"],"via":{"orpha":99854,"name":"Cree leukoencephalopathy"}},{"symbol":"EIF2B5","name":"eukaryotic translation initiation factor 2B subunit epsilon","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3261","ensembl":"ENSG00000145191","omim":"603945","loci":["3q27.1"],"via":{"orpha":157713,"name":"Congenital or early infantile CACH syndrome"}},{"symbol":"EIF2B5","name":"eukaryotic translation initiation factor 2B subunit epsilon","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3261","ensembl":"ENSG00000145191","omim":"603945","loci":["3q27.1"],"via":{"orpha":157716,"name":"Late infantile CACH syndrome"}},{"symbol":"EIF2B5","name":"eukaryotic translation initiation factor 2B subunit epsilon","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301435[PMID]","hgnc":"3261","ensembl":"ENSG00000145191","omim":"603945","loci":["3q27.1"],"via":{"orpha":157719,"name":"Juvenile or adult CACH syndrome"}}],"inheritance":["Autosomal recessive"],"onset":["Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":148.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-12-18","source":"29740943[PMID]_20301435[PMID]","terms":[{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006978","label":"Dysmyelinating leukodystrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007366","label":"Atrophy/Degeneration affecting the brainstem","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006855","label":"Cerebellar vermis atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002070","label":"Limb ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008209","label":"Premature ovarian insufficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002344","label":"Progressive neurologic deterioration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002078","label":"Truncal ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007361","label":"Abnormality of the pons","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000741","label":"Apathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002804","label":"Arthrogryposis multiplex congenita","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000618","label":"Blindness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001558","label":"Decreased fetal movement","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032398","label":"Dysgyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001310","label":"Dysmetria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0033049","label":"Globus pallidus hypointensity on susceptibility-weighted imaging","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000133","label":"Gonadal dysgenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002315","label":"Headache","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001269","label":"Hemiparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006956","label":"Lateral ventricle dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002076","label":"Migraine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011342","label":"Mild global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008288","label":"Nonketotic hyperglycinemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001562","label":"Oligohydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100653","label":"Optic neuritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001733","label":"Pancreatitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000786","label":"Primary amenorrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000089","label":"Renal hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000869","label":"Secondary amenorrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001264","label":"Spastic diplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012690","label":"T2 hypointense thalamus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012704","label":"Widened subarachnoid space","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004481","label":"Progressive macrocephaly","frequency":"Very rare (<4-1%)","criteria":null}]}}