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Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder. Genetic analysis revealed a homozygous c.1338delG <jats:italic>MOCS1<\/jats:italic> mutation causing a frameshift (p.S442fs) with a premature termination of the MOCS1AB translation product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine analysis detected trace amounts (1% of control) of the Moco degradation product urothione, suggesting a residual Moco synthesis in the patient, which was consistent with the mild clinical presentation. Therefore, we performed bioinformatic analysis of the patient's mutated <jats:italic>MOCS1<\/jats:italic> transcript and found a potential Kozak\u2010sequence downstream of the mutation site providing the possibility of an independent expression of a MOCS1B protein. Following the expression of the patient's <jats:italic>MOCS1<\/jats:italic> cDNA in HEK293 cells we detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B. Functional studies of both proteins confirmed activity of MOCS1B, but not of the truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation re\u2010initiation in the <jats:italic>MOCS1<\/jats:italic> transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms of MoCD.<\/jats:p>","DOI":"10.1007\/s10545-018-0138-7","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T08:20:43Z","timestamp":1516782043000},"page":"187-196","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation"],"prefix":"10.1002","volume":"41","author":[{"given":"Simon Julius","family":"Mayr","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry University of Cologne Z\u00fclpicher Str. 47 K\u00f6ln 50674 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rn Oliver","family":"Sass","sequence":"additional","affiliation":[{"name":"Bioanalytics &amp; Biochemistry, Department of Natural Science Bonn\u2010Rhein Sieg University of Applied Sciences Rheinbach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Vry","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine Medical Center \u2013 University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janbernd","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine Medical Center \u2013 University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Mader","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Neuroradiology University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u2010Bernd","family":"H\u00f6vener","sequence":"additional","affiliation":[{"name":"Department of Radiology, Medical Physics, Faculty of Medicine Medical Center \u2013 University of Freiburg, University of Freiburg Freiburg Germany"},{"name":"Section for Biomedical Imaging and MOIN CC University Medical Center Schleswig Holstein, University of Kiel Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Reiss","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Universit\u00e4t G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Angel","family":"Santamaria\u2010Araujo","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry University of Cologne Z\u00fclpicher Str. 47 K\u00f6ln 50674 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Chemistry University of Cologne Z\u00fclpicher Str. 47 K\u00f6ln 50674 Germany"},{"name":"Center for Molecular Medicine Cologne) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Catharina","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine Medical Center \u2013 University of Freiburg Mathildenstr. 1 Freiburg 79106 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1151-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.11.010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121078"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_89"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb32915.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.011"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01805591"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-4-2-119"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a129054"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.3.860"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355838200000182"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.06.011"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200947200"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja401781t"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1500697112"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1998.tb15357.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38240"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.22.6856"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113974"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","unstructured":"JohnsonJL RajagopalanKV WadmanSK(1993)Human Molybdenum Cofactor Deficiency.In:AylingJE NairMG Baugh CM (eds) Advances in experimental medicine and biology: chemistry and biology of pteridines and folates. 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