{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:22Z","timestamp":1790710162536,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,4,4]],"date-time":"2008-04-04T00:00:00Z","timestamp":1207267200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year\u2010old girl born to consanguineous parents. Blood manganese levels were &gt;3000 nmol\/L (normal range &lt;320 nmol\/L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease. In order to assess the genetic basis of this syndrome we investigated two candidate genes: <jats:italic>ATP2C2<\/jats:italic> and <jats:italic>ATP2A3<\/jats:italic> encoding the manganese\u2010transporting calcium\u2010ATPases, SPCA2 and SERCA3, respectively. Genotyping of the patient and the family for microsatellite markers surrounding <jats:italic>ATP2C2<\/jats:italic> and <jats:italic>ATP2A3<\/jats:italic> excluded these genes. The patient was found to be heterozygous for both gene loci. Despite the unknown pathophysiology, we were able to develop a successful treatment regime. Chelation therapy with disodium calcium edetate combined with iron supplementation is the treatment of choice, lowering blood manganese levels significantly and improving clinical symptoms.<\/jats:p>","DOI":"10.1007\/s10545-008-0813-1","type":"journal-article","created":{"date-parts":[[2008,4,7]],"date-time":"2008-04-07T01:29:41Z","timestamp":1207531781000},"page":"151-163","source":"Crossref","is-referenced-by-count":127,"title":["Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia\u2014A new metabolic disorder"],"prefix":"10.1002","volume":"31","author":[{"given":"Karin","family":"Tuschl","sequence":"first","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa B.","family":"Mills","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Parsons","sequence":"additional","affiliation":[{"name":"Paediatric Gastroenterology and Nutrition Shaikh Khalifa Medical Centre Shaikh Khalifa United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Malone","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Fowler","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bitner\u2010Glindzicz","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Clayton","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health with Great Ormond Street Hospital for Children NHS Trust London UK"},{"name":"Biochemistry Research Group, Clinical and Molecular Genetics Unit UCL Institute of Child Health 30 Guilford Street London WC1N 1EH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,4,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61782-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-006-9030-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840160613"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00554a015"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0243-2"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21321"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2007.01.003"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.931"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.8.658"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/122.6.1300"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306784200"},{"key":"e_1_2_6_13_1","volume-title":"An Introduction to Atomic Absorption Spectroscopy\u2014A Self Teaching Approach","author":"Ebdon L","year":"1982"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1864"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm044"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)90735-7"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:MEBR.0000043973.10494.85"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.11.013"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.016766"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(86)90575-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.83.5.439"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/41343"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(02)00016-5"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(03)00026-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2006.10.005"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(82)90201-6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.9.1385"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2004.04.001"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004200050414"},{"key":"e_1_2_6_30_1","first-page":"287","article-title":"Long\u2010term exposure to \u201clow levels\u201d of manganese oxides and neurofunctional changes in ferroalloy workers","volume":"20","author":"Lucchini R","year":"1999","journal-title":"Neurotoxicology"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.19.10.1000"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/enrs.1997.3710"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-191"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.03.031"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002340050333"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602006000100006"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/75.1.112"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00135.2004"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110612200"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.2.270"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.08.018"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051298"},{"key":"e_1_2_6_44_1","first-page":"409","article-title":"Ccute manganese overload. A new experimental model of intrahepatic cholestasis","volume":"53","author":"Witzleben CL","year":"1968","journal-title":"Am J Pathol"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413116200"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0813-1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-008-0813-1","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0813-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T09:26:13Z","timestamp":1694769973000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-008-0813-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,4]]}},"alternative-id":["10.1007\/s10545-008-0813-1"],"URL":"https:\/\/doi.org\/10.1007\/s10545-008-0813-1","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4]]}}}