{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:41:18Z","timestamp":1788424878664,"version":"build-2803163510"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2023-0049_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>DNAJC12 deficiency (OMIM# 617384) is a new cause of hyperphenylalaninemia (HPA). The deficiency of the co-chaperone protein DNAJC12 was identified in 2017. To date, only 43 patients have been reported. Here, we report four patients from a single family with DNAJC12 deficiency while being followed up with a diagnosis of HPA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0049_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>Two of the patients, who were cousins, were diagnosed with HPA by newborn screening. And the other two patients were siblings of these patients. Neurological examinations were normal except for one patient with mild learning disability. A c.158-2A&gt;T p.(?) biallelic pathogenic variant was detected in intron 2 of the <jats:italic>DNAJC12<\/jats:italic> gene. In the 24\u00a0h tetrahydrobiopterin (BH4) challenge test, there was a significant decrease in phenylalanine levels, especially at the 16th hour. Three patients had decreased homovalinic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in cerebrospinal fluid (CSF), while only one had decreased 5HIAA. In treatment, sapropterin, levodopa\/carbidopa and 5-OH tryptophan were started.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0049_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We propose that it will be beneficial to evaluate the patients who have unexplained hyperphenylalaninemia for DNAJC12 deficiency. Patients with early diagnosis of neurotransmitter deficiency may be given a chance to be treated before clinical symptoms begin.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2023-0049","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T10:50:30Z","timestamp":1686135030000},"page":"791-797","source":"Crossref","is-referenced-by-count":6,"title":["A rare cause of hyperphenylalaninemia: four cases from a single family with DNAJC12 deficiency"],"prefix":"10.1515","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0112-0624","authenticated-orcid":false,"given":"Dilek","family":"Gunes","sequence":"first","affiliation":[{"name":"Division of Inborn Metabolic Disease, Department of Pediatrics , Bezmialem Vakif University Hospital , \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyli","family":"Senturk","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics , Istanbul Bagcilar Training and Research Hospital , \u0130stanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"2023080909320500040_j_jpem-2023-0049_ref_001","doi-asserted-by":"crossref","unstructured":"Blau, N, Martinez, A, Hoffmann, GF, Th\u00f6ny, B. DNAJC12 deficiency: a new strategy in the diagnosis of hyperphenylalaninemias. Mol Genet Metabol 2018;123:1\u20135. https:\/\/doi.org\/10.1016\/j.ymgme.2017.11.005.","DOI":"10.1016\/j.ymgme.2017.11.005"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_002","doi-asserted-by":"crossref","unstructured":"Anikster, Y, Haack, TB, Vilboux, T, Pode-Shakked, B, Thony, B, Shen, N, et al.. Biallelic mutations in DNAJC12 cause hyperphenylalaninemia, dystonia, and intellectual disability. Am J Hum Genet 2017;100:257\u201366. https:\/\/doi.org\/10.1016\/j.ajhg.2017.01.002.","DOI":"10.1016\/j.ajhg.2017.01.002"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_003","doi-asserted-by":"crossref","unstructured":"Jung-Kc, K, Himmelreich, N, Presteg\u00e5rd, KS, Shi, TS, Scherer, T, Ying, M, et al.. Phenylalanine hydroxylase variants interact with the co-chaperone DNAJC12. Hum Mutat 2019;40:483\u201394. https:\/\/doi.org\/10.1002\/humu.23712.","DOI":"10.1002\/humu.23712"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_004","doi-asserted-by":"crossref","unstructured":"Straniero, L, Guella, I, Cilia, R, Parkkinen, L, Rimoldi, V, Young, A, et al.. DNAJC12 and dopa-responsive non-progressive parkinsonism. Ann Neurol 2017;82:640\u20136. https:\/\/doi.org\/10.1002\/ana.25048.","DOI":"10.1002\/ana.25048"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_005","doi-asserted-by":"crossref","unstructured":"van Spronsen, FJ, Himmelreich, N, Rufenacht, V, Shen, N, Vliet, DV, Al-Owain, M, et al.. Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: from attention deficit to severe dystonia and intellectual disability. J Med Genet 2017. https:\/\/doi.org\/10.1136\/jmedgenet-2017-104875.","DOI":"10.1136\/jmedgenet-2017-104875"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_006","doi-asserted-by":"crossref","unstructured":"Veenma, D, Cordeiro, D, Sondheimer, N, Mercimek-Andrews, S. DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis. Eur J Hum Genet 2018;26:1867\u201370. https:\/\/doi.org\/10.1038\/s41431-018-0237-9.","DOI":"10.1038\/s41431-018-0237-9"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_007","doi-asserted-by":"crossref","unstructured":"de Sain-van der Velden, MGM, Kuper, WFE, Kuijper, MA, van Kats, LAT, Prinsen, HCMT, Balemans, ACJ, et al.. Beneficial effect of BH4 treatment in a 15-year-old boy with biallelic mutations in DNAJC12. JIMD Rep 2018;42:99\u2013103. https:\/\/doi.org\/10.1007\/8904_2017_86.","DOI":"10.1007\/8904_2017_86"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_008","doi-asserted-by":"crossref","unstructured":"Brennenstuhl, H, Jung-Klawitter, S, Assmann, B, Opladen, T. Inherited disorders of neurotransmitters: classification and practical approaches for diagnosis and treatment. Neuropediatrics 2019;50:2\u201314. https:\/\/doi.org\/10.1055\/s-0038-1673630.","DOI":"10.1055\/s-0038-1673630"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_009","doi-asserted-by":"crossref","unstructured":"Feng, Y, Liu, S, Tang, C, Jiang, X, Tang, F, Li, B, et al.. Identification of an inherited pathogenic DNAJC12 variant in a patient with hyperphenylalalinemia. Clin Chim Acta 2019;490:172\u20135. https:\/\/doi.org\/10.1016\/j.cca.2018.09.002.","DOI":"10.1016\/j.cca.2018.09.002"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_010","doi-asserted-by":"crossref","unstructured":"Li, M, Yang, Q, Yi, S, Qin, Z, Luo, J, Fan, X. Two novel mutations in DNAJC12\u00a0identified by whole-exome sequencing in a patient with\u00a0mild\u00a0hyperphenylalaninemia. Mol Genet Genomic Med 2020;8:e1303. https:\/\/doi.org\/10.1002\/mgg3.1303.","DOI":"10.1002\/mgg3.1303"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_011","doi-asserted-by":"crossref","unstructured":"Gallego, D, Leal, F, G\u00e1mez, A, Castro, M, Navarrete, R, Sanchez-Lijarcio, O, et al.. Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. Hum Mutat 2020;7:1329\u201338. https:\/\/doi.org\/10.1002\/humu.24026.","DOI":"10.1002\/humu.24026"},{"key":"2023080909320500040_j_jpem-2023-0049_ref_012","doi-asserted-by":"crossref","unstructured":"\u00c7\u0131k\u0131, K, Y\u0131ld\u0131z, Y, Y\u00fccel Y\u0131lmaz, D, Pekta\u015f, E, Tokatl\u0131, A, \u00d6zg\u00fcl, RK, et al.. DNACJ12 deficiency in patients with unexplained hyperphenylalaninemia: two new patients and a novel variant. Metab Brain Dis 2021;36:1405\u201310. https:\/\/doi.org\/10.1007\/s11011-021-00753-0.","DOI":"10.1007\/s11011-021-00753-0"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0049\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T09:33:15Z","timestamp":1691573595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2023-0049\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,7]]},"references-count":12,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,6,22]]},"published-print":{"date-parts":[[2023,8,28]]}},"alternative-id":["10.1515\/jpem-2023-0049"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2023-0049","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,7]]}}}