{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:46:39Z","timestamp":1781333199816,"version":"3.54.1"},"reference-count":31,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Only scarce information is available on the long-term outcome and the natural course of children with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) due to mutations in the IGHMBP2 gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>To describe the natural disease course, to systematically quantify the residual capacities of children with SMARD1 who survive on permanent mechanical respiration, and to identify markers predicting the disease outcome at the time of manifestation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>We conducted a longitudinal study of 11 infantile SMARD1 patients over a mean observational period of 7.8 (SD 3.2) years. Disease-specific features were continuously assessed by using a semiquantitative scoring system. Additionally, we analyzed the residual enzymatic activity of 6 IGHMBP2 mutants in our patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>After an initial rapid decline of the clinical score until the age of 2 years, residual capabilities reached a plateau or even improved. The overall clinical outcome was markedly heterogeneous, but clinical scores at the age of 3 months showed a positive linear correlation with the clinical outcome at 1 year and at 4 years of age. If expressed in an in vitro recombinant system, mutations of patients with more favorable outcomes retained residual enzymatic activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Despite their severe disabilities and symptoms, most SMARD1 patients are well integrated into their home environment and two thirds of them are able to attend kindergarten or school. This information will help to counsel parents at the time of disease manifestation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2011-0544","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T02:11:45Z","timestamp":1323742305000},"page":"e148-e156","source":"Crossref","is-referenced-by-count":66,"title":["The Natural Course of Infantile Spinal Muscular Atrophy With Respiratory Distress Type 1 (SMARD1)"],"prefix":"10.1542","volume":"129","author":[{"given":"Maria","family":"Eckart","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf-Peter","family":"Guenther","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Idkowiak","sequence":"additional","affiliation":[{"name":"Children\u00b4s Hospital, Technical University, Dresden, Germany,"},{"name":"Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymonda","family":"Varon","sequence":"additional","affiliation":[{"name":"Institute for Medical and Human Genetics, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Grolle","sequence":"additional","affiliation":[{"name":"Altonaer Kinderkrankenhaus, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Boffi","sequence":"additional","affiliation":[{"name":"Department of Child Neuropsychiatry, University of Turin, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Van Maldergem","sequence":"additional","affiliation":[{"name":"Centre de g\u00e9n\u00e9tique humaine, Universit\u00e9 de Franche-Comt\u00e9, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics,"},{"name":"NeuroCure Clinical Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"von Au","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"issue":"1","key":"2021120902571569000_B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/ng703","article-title":"Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1","volume":"29","author":"Grohmann","year":"2001","journal-title":"Nat Genet"},{"issue":"6","key":"2021120902571569000_B2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ana.10755","article-title":"Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"54","author":"Grohmann","year":"2003","journal-title":"Ann Neurol"},{"issue":"Pt 12","key":"2021120902571569000_B3","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1093\/brain\/awg278","article-title":"Severe infantile neuropathy with diaphragmatic weakness and its relationship to SMARD1","volume":"126","author":"Pitt","year":"2003","journal-title":"Brain"},{"issue":"8","key":"2021120902571569000_B4","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/humu.20525","article-title":"Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis","volume":"28","author":"Guenther","year":"2007","journal-title":"Hum Mutat"},{"issue":"2","key":"2021120902571569000_B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/0883073807310989","article-title":"Spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"23","author":"Kaindl","year":"2008","journal-title":"J Child Neurol"},{"issue":"3","key":"2021120902571569000_B6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.sbi.2010.03.011","article-title":"SF1 and SF2 helicases: family matters","volume":"20","author":"Fairman-Williams","year":"2010","journal-title":"Curr Opin Struct Biol"},{"issue":"18","key":"2021120902571569000_B7","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/hmg\/ddh222","article-title":"Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"13","author":"Grohmann","year":"2004","journal-title":"Hum Mol Genet"},{"issue":"11","key":"2021120902571569000_B8","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/hmg\/ddh129","article-title":"Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy","volume":"13","author":"Maddatu","year":"2004","journal-title":"Hum Mol Genet"},{"issue":"23","key":"2021120902571569000_B9","doi-asserted-by":"crossref","first-page":"17463","DOI":"10.1016\/S0021-9258(19)85357-7","article-title":"The human S mu bp-2, a DNA-binding protein specific to the single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region","volume":"268","author":"Fukita","year":"1993","journal-title":"J Biol Chem"},{"issue":"37","key":"2021120902571569000_B10","doi-asserted-by":"crossref","first-page":"21503","DOI":"10.1074\/jbc.270.37.21503","article-title":"Molecular characterization of the rat insulin enhancer-binding complex 3b2. Cloning of a binding factor with putative helicase motifs","volume":"270","author":"Shieh","year":"1995","journal-title":"J Biol Chem"},{"issue":"1","key":"2021120902571569000_B11","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/viro.1998.9588","article-title":"Smubp-2 represses the Epstein-Barr virus lytic switch promoter","volume":"255","author":"Zhang","year":"1999","journal-title":"Virology"},{"issue":"12","key":"2021120902571569000_B12","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1093\/hmg\/ddp134","article-title":"Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery","volume":"18","author":"de Planell-Saguer","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"7","key":"2021120902571569000_B13","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1093\/hmg\/ddp028","article-title":"IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1)","volume":"18","author":"Guenther","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"5","key":"2021120902571569000_B14","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1086\/302636","article-title":"Diaphragmatic spinal muscular atrophy with respiratory distress is heterogeneous, and one form Is linked to chromosome 11q13-q21","volume":"65","author":"Grohmann","year":"1999","journal-title":"Am J Hum Genet"},{"issue":"5","key":"2021120902571569000_B15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/humu.9241","article-title":"Allelic heterogeneity of SMARD1 at the IGHMBP2 locus","volume":"23","author":"Maystadt","year":"2004","journal-title":"Hum Mutat"},{"issue":"6","key":"2021120902571569000_B16","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/1531-8249(200012)48:6<877::AID-ANA8>3.0.CO;2-#","article-title":"A novel form of distal hereditary motor neuronopathy maps to chromosome 9p21.1-p12","volume":"48","author":"Christodoulou","year":"2000","journal-title":"Ann Neurol"},{"issue":"6","key":"2021120902571569000_B17","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/sj.ejhg.5201177","article-title":"Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families","volume":"12","author":"Viollet","year":"2004","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"2021120902571569000_B18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1086\/518900","article-title":"The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset","volume":"81","author":"Maystadt","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"5","key":"2021120902571569000_B19","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1086\/375039","article-title":"Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V","volume":"72","author":"Antonellis","year":"2003","journal-title":"Am J Hum Genet"},{"issue":"1","key":"2021120902571569000_B20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00109-008-0402-7","article-title":"Clinical variability in distal spinal muscular atrophy type 1 (DSMA1): determination of steady-state IGHMBP2 protein levels in five patients with infantile and juvenile disease","volume":"87","author":"Guenther","year":"2009","journal-title":"J Mol Med (Berl)"},{"issue":"3","key":"2021120902571569000_B21","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1055\/s-2004-820994","article-title":"Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"35","author":"Rudnik-Sch\u00f6neborn","year":"2004","journal-title":"Neuropediatrics"},{"issue":"8","key":"2021120902571569000_B22","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/j.1469-8749.2004.tb01019.x","article-title":"Congenital peripheral neuropathy presenting as apnoea and respiratory insufficiency: spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"46","author":"Appleton","year":"2004","journal-title":"Dev Med Child Neurol"},{"issue":"11","key":"2021120902571569000_B23","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1007\/s00134-006-0346-8","article-title":"Respiratory failure in infants due to spinal muscular atrophy with respiratory distress type 1","volume":"32","author":"Giannini","year":"2006","journal-title":"Intensive Care Med"},{"issue":"6","key":"2021120902571569000_B24","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.pediatrneurol.2005.10.022","article-title":"Mutation of gene in spinal muscular atrophy respiratory distress type I","volume":"34","author":"Wong","year":"2006","journal-title":"Pediatr Neurol"},{"issue":"4","key":"2021120902571569000_B25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00439-004-1156-0","article-title":"Genomic rearrangements at the IGHMBP2 gene locus in two patients with SMARD1","volume":"115","author":"Guenther","year":"2004","journal-title":"Hum Genet"},{"issue":"3","key":"2021120902571569000_B26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.nmd.2008.11.013","article-title":"Interfamilial phenotypic heterogeneity in SMARD1","volume":"19","author":"Joseph","year":"2009","journal-title":"Neuromuscul Disord"},{"issue":"6","key":"2021120902571569000_B27","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1177\/0883073809344121","article-title":"Infantile spinal muscular atrophy with respiratory distress type 1: a case report","volume":"25","author":"AlSaman","year":"2010","journal-title":"J Child Neurol"},{"issue":"5","key":"2021120902571569000_B28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/PHM.0b013e31804a8505","article-title":"Long-term survival in Werdnig-Hoffmann disease","volume":"86","author":"Bach","year":"2007","journal-title":"Am J Phys Med Rehabil"},{"issue":"4","key":"2021120902571569000_B29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1089\/pai.2009.0002","article-title":"Spinal muscular atrophy type 1: prolongation of survival by noninvasive respiratory aids","volume":"22","author":"Bach","year":"2009","journal-title":"Pediatr Asthma Allergy Immunol"},{"issue":"21","key":"2021120902571569000_B30","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1093\/hmg\/ddi349","article-title":"Dilated cardiomyopathy in the nmd mouse: transgenic rescue and QTLs that improve cardiac function and survival","volume":"14","author":"Maddatu","year":"2005","journal-title":"Hum Mol Genet"},{"issue":"1","key":"2021120902571569000_B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000007039","article-title":"Cardiac involvement in primary myopathies","volume":"94","author":"Finsterer","year":"2000","journal-title":"Cardiology"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/129\/1\/e148\/1056848\/peds_2011-0544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/129\/1\/e148\/1056848\/peds_2011-0544.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T16:18:07Z","timestamp":1639066687000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/129\/1\/e148\/31582\/The-Natural-Course-of-Infantile-Spinal-Muscular"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1,1]]},"published-print":{"date-parts":[[2012,1,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2011-0544","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,1]]}}}