{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:14:13Z","timestamp":1783419253789,"version":"3.54.6"},"reference-count":16,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Biallelic pathogenic variants in DNAJC30 cause an autosomal recessive form of Leber hereditary optic neuropathy (LHONAR1), traditionally considered a mitochondrially transmitted disorder. The phenotypic spectrum of diseases linked to DNAJC30 includes isolated optic neuropathy, Leigh syndrome spectrum (LSS), and atypical LHON-plus. Case description: Here, we report a 13-year-old boy presenting symptoms of area postrema syndrome (APS), with recurrent vomiting, vertigo, nystagmus, and subacute visual deterioration with central scotoma. Ophthalmological examination revealed bilateral papilledema with telangiectatic vessels, while visual evoked potentials demonstrated severe bilateral optic pathway dysfunction. Brain magnetic resonance imaging (MRI) showed T2\/FLAIR hyperintense lesions involving the area postrema and enhancement of the optic nerves, strongly suggesting seronegative neuromyelitis optica spectrum disorder (NMOSD). Extensive immunological and cerebrospinal fluid studies, including anti-aquaporin-4 (AQP4) and anti-MOG antibodies, were negative. High-dose corticosteroids and intravenous immunoglobulins resulted in only transient and incomplete improvement, followed by further visual decline. Additionally, laboratory tests detected elevated lactate plasma levels. Hence, whole-exome sequencing was performed, which identified a homozygous pathogenic DNAJC30 c.152A&gt;G, p.(Tyr51Cys) variant, associated with LHONAR1. After initiation of idebenone therapy, the patient showed significant improvement in visual function, normalization of lactate levels, and complete resolution of the brainstem lesions on follow-up MRI. Conclusions: This case further expands the neuro-ophthalmic spectrum associated with DNAJC30 variants and suggests that DNAJC30-related disease may closely mimic seronegative NMOSD. We highlight that early genetic diagnosis is essential, as recognition of this mitochondrial etiology enables targeted therapy and may substantially improve clinical outcomes.<\/jats:p>","DOI":"10.3390\/jcm15135289","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:04:49Z","timestamp":1783411489000},"page":"5289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When LHON Mimics Demyelination: Area Postrema Syndrome in Biallelic DNAJC30 Variants"],"prefix":"10.3390","volume":"15","author":[{"given":"Kamil","family":"Dzwilewski","sequence":"first","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Krygier","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Szymarek","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-1882","authenticated-orcid":false,"given":"Marta","family":"Zawadzka","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7153-6190","authenticated-orcid":false,"given":"Urszula","family":"Stodolska-Koberda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-5066","authenticated-orcid":false,"given":"Maria","family":"Mazurkiewicz-Be\u0142dzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gdansk, ul. D\u0119binki 7, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.cell.2018.09.014","article-title":"The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development","volume":"175","author":"Tebbenkamp","year":"2018","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e138267","DOI":"10.1172\/JCI138267","article-title":"Impaired complex I repair causes recessive Leber\u2019s hereditary optic neuropathy","volume":"131","author":"Stenton","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1093\/brain\/awac052","article-title":"DNAJC30 defect: A frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome","volume":"145","author":"Stenton","year":"2022","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/cge.14196","article-title":"Expanding the phenotype of DNAJC30-associated Leigh syndrome","volume":"102","author":"Zawadzka","year":"2022","journal-title":"Clin. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1007\/s00415-023-11673-7","article-title":"Additive effect of DNAJC30 and NDUFA9 mutations causing Leigh syndrome","volume":"270","author":"Nesti","year":"2023","journal-title":"J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.gendis.2022.09.011","article-title":"A homozygous nonsense mutation in DNAJC30 causes Leber\u2019s hereditary optic neuropathy with Leigh-like phenotypes","volume":"10","author":"Shen","year":"2023","journal-title":"Genes Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"468","DOI":"10.5603\/pjnns.100423","article-title":"Effects of idebenone treatment in a patient with DNAJC30-associated Leigh Syndrome","volume":"58","author":"Dzwilewski","year":"2024","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e63902","DOI":"10.1002\/ajmg.a.63902","article-title":"An Unusual Presentation of Leber Hereditary Optic Neuropathy-Plus Case Caused by a Novel DNAJC30 Variant","volume":"197","author":"Soydemir","year":"2025","journal-title":"Am. J. Med. Genet A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1136\/jmedgenet-2021-108235","article-title":"DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber\u2019s hereditary optic neuropathy and optic atrophy","volume":"59","author":"Kieninger","year":"2022","journal-title":"J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Skorczyk-Werner, A., To\u0144ska, K., Maciejczuk, A., Nowomiejska, K., Korwin, M., O\u0142dak, M., Wawrocka, A., and Krawczy\u0144ski, M.R. (2023). DNAJC30 Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417496"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jnnp-2012-304426","article-title":"A guide to diagnosis and treatment of Leigh syndrome","volume":"85","author":"Baertling","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1093\/brain\/awae057","article-title":"Digenic Leigh syndrome on the background of the","volume":"147","author":"Stenton","year":"2024","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1093\/brain\/awad131","article-title":"Autosomal recessive Leber hereditary optic neuropathy, a new neuro-ophthalmo-genetic paradigm","volume":"146","author":"Lenaers","year":"2023","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e238588","DOI":"10.1136\/bcr-2020-238588","article-title":"Area postrema syndrome: A neurological presentation of nausea, vomiting and hiccups","volume":"13","author":"Chan","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rahimi, G., Silverman, M., Lucas, M., Kazerooni, L., Yousuf, M.M., Jafarpour, S., and Santoro, J.D. (2025). Leber\u2019s hereditary optic neuropathy and multiple sclerosis: Overlap between mitochondrial disease and neuroinflammation. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1538358"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/5289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:24:35Z","timestamp":1783416275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/5289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":16,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15135289"],"URL":"https:\/\/doi.org\/10.3390\/jcm15135289","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]}}}