{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:52:02Z","timestamp":1790175122486,"version":"4.1.0"},"reference-count":106,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004350","name":"Studienstiftung des Deutschen Volkes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autophagy is a fundamental and conserved catabolic pathway that mediates the degradation of macromolecules and organelles in lysosomes. Autophagy is particularly important to postmitotic and metabolically active cells such as neurons. The complex architecture of neurons and their long axons pose additional challenges for efficient recycling of cargo. Not surprisingly autophagy is required for normal central nervous system development and function. Several single\u2010gene disorders of the autophagy pathway have been discovered in recent years giving rise to a novel group of inborn errors of metabolism referred to as <jats:italic>congenital disorders of autophagy<\/jats:italic>. While these disorders are heterogeneous, they share several clinical and molecular characteristics including a prominent and progressive involvement of the central nervous system leading to brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and cognitive decline. On brain magnetic resonance imaging a predominant involvement of the corpus callosum, the corticospinal tracts and the cerebellum are noted. A storage disease phenotype is present in some diseases, underscoring both clinical and molecular overlaps to lysosomal storage diseases. This review provides an update on the clinical, imaging, and genetic spectrum of congenital disorders of autophagy and highlights the importance of this pathway for neurometabolism and childhood\u2010onset neurological diseases.<\/jats:p>","DOI":"10.1002\/jimd.12084","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T02:24:30Z","timestamp":1552271070000},"page":"51-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Novel insights into the clinical and molecular spectrum of congenital disorders of autophagy"],"prefix":"10.1002","volume":"43","author":[{"given":"Julian","family":"Teinert","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Behne","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi\u2010Fakhari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0092-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0037-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1608652"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv371"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.048"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.03.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.01.022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170055"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060815-014556"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7120278"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796697"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.054"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1277310"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1100356"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.03.025"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.146365"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv393"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0399-x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36753"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201211014"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38676"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","unstructured":"Kane MS Zhao J Muskett J Diplock A Srivastava S Hauser N Deeken JF Niederhuber JE Smith WE Vilboux T Ebrahimi\u2010Fakhari D. EPG5 variants with modest functional impact result in an ameliorated and primarily neurological phenotype in a 3.5\u2010year\u2010old patient with Vici syndrome.In Press. 2019.","DOI":"10.1055\/s-0039-1692129"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2497"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.04.034"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.24856"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02840-8"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.08.021"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00041-7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1980"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.03.004"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27491"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5935"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77598"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000098"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu121"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000408"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.64"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003988"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1507438"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12730"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.09.015"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.191"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09204"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695189"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.09.010"},{"key":"e_1_2_10_47_1","volume-title":"GeneReviews(R)","author":"Ebrahimi\u2010Fakhari D","year":"2018"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38561"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12028"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.8.2787"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.01.015"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12465"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010591200"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06172-7"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007363"},{"key":"e_1_2_10_56_1","article-title":"AP\u20104 mediated ATG9A sorting underlies axonal and autophagosome biogenesis defects in a mouse model of AP\u20104 deficiency syndrome","author":"Ivankovic D","year":"2017","journal-title":"bioRxiv"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717327114"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3256"},{"issue":"10","key":"e_1_2_10_59_1","first-page":"670","article-title":"Exome sequencing and linkage analysis identified novel candidate genes in recessive intellectual disability associated with ataxia","volume":"18","author":"Jazayeri R","year":"2015","journal-title":"Arch Iran Med"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.11.006"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.10.007"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy101"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2005.tb01902.x"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04724"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12245"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63233-3.00019-1"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.159"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.019"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.27"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2562"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.274"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13957"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.07.002"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt095"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000227"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.18"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36779"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.01.020"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2013.11.019"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1571189"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25868"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.CPJ.0000437694.17888.9b"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2677"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005564"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1359381"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15637"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-09-0746"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.06.024"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1047127"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy230"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.026"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005869"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170035"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.8.13426"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.09.034"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.03.016"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.016"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25130"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000076"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38019"},{"key":"e_1_2_10_101_1","article-title":"Further delineation of TBCK \u2010 infantile hypotonia with psychomotor retardation and characteristic facies type 3","author":"Zapata\u2010Aldana E","year":"2018","journal-title":"Eur J Med Genet"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0646-6"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.06.001"},{"key":"e_1_2_10_104_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201401070"},{"key":"e_1_2_10_105_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701311104"},{"key":"e_1_2_10_106_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4964"},{"key":"e_1_2_10_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04723"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjimd.12084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T05:15:04Z","timestamp":1693286104000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,8]]},"references-count":106,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/jimd.12084"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12084","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,8]]},"assertion":[{"value":"2019-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}