{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:29:10Z","timestamp":1783542550899,"version":"3.55.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neonatal-onset movement disorders, especially in combination with seizures, are rare and often related to mitochondrial disorders. 3-methylglutaconic aciduria (3-MGA-uria) is a marker for mitochondrial dysfunction. In particular, consistently elevated urinary excretion of 3-methylglutaconic acid is the hallmark of a small but growing group of inborn errors of metabolism (IEM) due to defective phospholipid remodeling or mitochondrial membrane-associated disorders (mutations in TAZ, SERAC1, OPA3, CLPB, DNAJC19, TMEM70, TIMM50). Exome\/genome sequencing is a powerful tool for the diagnosis of the clinically and genetically heterogeneous mitochondrial disorders. Here, we report 11 individuals, of whom 2 are previously unpublished, with biallelic variants in high temperature requirement protein A2 (HTRA2) encoding a mitochondria-localized serine protease. All individuals presented a recognizable phenotype with neonatal- or infantile-onset neurodegeneration and death within the first month of life. Hallmark features were central hypopnea\/apnea leading to respiratory insufficiency, seizures, neutropenia, 3-MGA-uria, tonus dysregulation, and dysphagia. Tremor, jitteriness, dystonia, and\/or clonus were also common. HTRA2 defect should be grouped under the IEM with 3-MGA-uria as discriminating feature. Clinical characteristics overlap with other disorders of this group suggesting a common underlying pathomechanism. Urinary organic acid analysis is a noninvasive and inexpensive test that can guide further genetic testing in children with suggestive clinical findings.<\/jats:p>","DOI":"10.1055\/s-0038-1667345","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T22:59:15Z","timestamp":1534460355000},"page":"373-378","source":"Crossref","is-referenced-by-count":15,"title":["HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy\u2014Report of 11 Patients"],"prefix":"10.1055","volume":"49","author":[{"given":"Gilles","family":"Morin","sequence":"first","affiliation":[{"name":"Service of Clinical Genetics, Amiens University Hospital, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nouri","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Science, Baghdad University, Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Brandau","sequence":"first","affiliation":[{"name":"Centogene AG, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebal","family":"Saadi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Children Welfare Teaching Hospital, Baghdad University, Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Nouri","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Science, Baghdad University, Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"van den Broek","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken, Paracelsus Medical University, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Prokisch","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"Institute of Human Genetics, Helmholtz Zentrum M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Mayr","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Salzburger Landeskliniken, Paracelsus Medical University, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Wortmann","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"Department of Pediatrics, Salzburger Landeskliniken, Paracelsus Medical University, Salzburg, Austria"},{"name":"Institute of Human Genetics, Helmholtz Zentrum M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reka","family":"Kovacs-Nagy","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2018,8,16]]},"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0038-1667345.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T23:33:19Z","timestamp":1542065599000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0038-1667345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,16]]},"references-count":0,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2018,11,12]]},"published-print":{"date-parts":[[2018,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0038-1667345","relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,16]]}}}