{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:56:42Z","timestamp":1760785002534},"reference-count":25,"publisher":"S.C. JURNALUL PENTRU MEDICINA SI VIATA S.R.L","issue":"3","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMedLife"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a spectrum of genetically and clinically heterogeneous diseases leading to the progressive degeneration of peripheric motor neurons with subsequent muscle weakness and atrophy. More than 95% of the cases of SMA are represented by homozygous mutations of the SMN1 gene (5q-SMA). Because this disease represents the leading cause of death due to a genetic cause and due to the availability of genetic therapies which can now save the life of the patient and stop the progress of the disease, early diagnosis is crucial. This report presents the case of a 13-year-old patient admitted to our hospital in 2018 who presented a phenotype typical to 5q-SMA. Next-generation sequencing (NGS) and Sanger sequencing of the SMN1 gene were performed, and a negative result was obtained. Consequently, we continued testing using whole-exome sequencing and discovered three mutations in the ASAH1 gene (one pathogenic and two variants of uncertain significance). Pathogenic mutations in the ASAH1 gene are responsible for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease, which overlapped with our patient\u2019s phenotype. Currently, there are 45 SMA cases caused by mutations in the ASAH1 gene reported worldwide; however, the present case is the first reported in Romania.<\/jats:p>","DOI":"10.25122\/jml-2021-0147","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T01:12:16Z","timestamp":1634260336000},"page":"424-428","source":"Crossref","is-referenced-by-count":9,"title":["Clinical features and genetics in non-5q spinal muscular atrophy caused by acid ceramidase deficiency"],"prefix":"10.25122","volume":"14","author":[{"given":"Mihaela","family":"Axente","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Pathophysiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena-Silvia","family":"Shelby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrada","family":"Mirea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Balneophysiokinetotherapy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Andrada Mirea, Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania E-mail: andrada.mirea@gmail.com","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Sporea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Balneophysiokinetotherapy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Badina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Pathophysiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Mihaela Badina, Department of Pathophysiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania E-mail: mihaela.badina@yahoo.com","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Padure","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dr. Nicolae Robanescu National Neurorehabilitation Center for Children, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Balneophysiokinetotherapy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Adriana","family":"Ion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Pathophysiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10755","published-online":{"date-parts":[[2021,6]]},"reference":[{"key":"ref1","unstructured":"Burr P, Reddivari AKR. Spinal Muscle Atrophy. StatPearls [Internet]. 2020;"},{"key":"ref2","unstructured":"Blueprint Genetics. Spinal Muscular Atrophy Panel [Internet]. Available from: https:\/\/blueprintgenetics.com\/tests\/panels\/neurology\/spinal-muscular-atrophy-panel\/"},{"key":"ref3","unstructured":"Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Mirzaa G, et al., editors. GeneReviews\u00ae [Internet] [Internet]. Seattle; 2000. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1352\/"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Shelby ES, Mirea A - Innovative therapies in genetic diseases: spinal muscular atrophy. Romanian Journal of Pediatrics - Vol. LXX, No. 2, pp 108\u2013113, 2021;","DOI":"10.37897\/RJP.2021.2.4"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Eggermann K, Gl\u00e4ser D, Abicht A, Wirth B. Spinal muscular atrophy (5qSMA): best practice of diagnostics, newborn screening and therapy. Medizinische Genet. 2020;32(3):263\u201372.","DOI":"10.1515\/medgen-2020-2033"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, et al. Prevalence, incidence and carrier frequency of 5q\u2013linked spinal muscular atrophy\u2013a literature review. Orphanet J Rare Dis. 2017;12(1):1\u201315.","DOI":"10.1186\/s13023-017-0671-8"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clin. 2015;33(4):831\u201346.","DOI":"10.1016\/j.ncl.2015.07.004"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies. Brain. 2014;137(11):2879\u201396.","DOI":"10.1093\/brain\/awu169"},{"key":"ref9","unstructured":"N-acylsphingosine amidohydrolase 1; ASAH1 [Internet]. Available from: https:\/\/omim.org\/entry\/613468"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Filosto M, Aureli M, Castellotti B, Rinaldi F, Schiumarini D, Valsecchi M, et al. ASAH1 variant causing a mild SMA phenotype with no myoclonic epilepsy: a clinical, biochemical and molecular study. Eur J Hum Genet. 2016;24(11):1578\u201383.","DOI":"10.1038\/ejhg.2016.28"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Li C-M, Park J-H, He X, Levy B, Chen F, Arai K, et al. The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression. Genomics. 1999;62(2):223\u201331.","DOI":"10.1006\/geno.1999.5940"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Bernardo K, Hurwitz R, Zenk T, Desnick RJ, Ferlinz K, Schuchman EH, et al. Purification, characterization, and biosynthesis of human acid ceramidase. J Biol Chem. 1995;270(19):11098\u2013102.","DOI":"10.1074\/jbc.270.19.11098"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Park J-H, Schuchman EH. Acid ceramidase and human disease. Biochim Biophys Acta (BBA)-Biomembranes. 2006;1758(12):2133\u20138.","DOI":"10.1016\/j.bbamem.2006.08.019"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Frohbergh M, He X, Schuchman EH. The molecular medicine of acid ceramidase. Biol Chem. 2015;396(6\u20137):759\u201365.","DOI":"10.1515\/hsz-2014-0290"},{"key":"ref15","unstructured":"Dyment DA, Bennett SAL, Medin JA, Levade T. ASAH1-related disorders. GeneReviews\u00ae[Internet]. 2018;"},{"key":"ref16","unstructured":"Yu FP, Amintas S, Levade T, Medin JA. Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis. 2018;13(1):1\u201319."},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Teoh HL, Solyom A, Schuchman EH, Mowat D, Roscioli T, Farrar M, et al. Polyarticular arthritis and spinal muscular atrophy in acid ceramidase deficiency. Pediatrics. 2016;138(4).","DOI":"10.1542\/peds.2016-1068"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Topaloglu H, Melki J. Spinal muscular atrophy associated with progressive myoclonus epilepsy. Epileptic Disord. 2016;18(s2):S128\u201334.","DOI":"10.1684\/epd.2016.0858"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Yildiz EP, Yesil G, Bektas G, Caliskan M, Tatl\u0131 B, Aydinli N, et al. Spinal muscular atrophy with progressive myoclonic epilepsy linked to mutations in ASAH1. Clin Neurol Neurosurg. 2018;164:47\u20139.","DOI":"10.1016\/j.clineuro.2017.11.008"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Cozma C, Iura\u0219cu M-I, Eichler S, Hovakimyan M, Brandau O, Zielke S, et al. C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease. Sci Rep. 2017;7(1):1\u201313.","DOI":"10.1038\/s41598-017-06604-2"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Kernohan KD, Fr\u00e9sard L, Zappala Z, Hartley T, Smith KS, Wagner J, et al. Whole-transcriptome sequencing in blood provides a diagnosis of spinal muscular atrophy with progressive myoclonic epilepsy. Hum Mutat. 2017;38(6):611\u20134.","DOI":"10.1002\/humu.23211"},{"key":"ref22","unstructured":"National Center for Biotechnology Information. NM_001267550.2(TTN):c.58137C>T (p.Cys19379=). ClinVar; [VCV000507035.2] [Internet]. Available from: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/507035\/ (accessed June 14, 2021)"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201323.","DOI":"10.1038\/gim.2015.30"},{"key":"ref24","unstructured":"National Center for Biotechnology Information. NM_177924.5(ASAH1):c.410_411del (p.Phe136_Tyr137insTer). ClinVar; [VCV000812471.1] [Internet]. Available from: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV000812471.1 (accessed June 14, 2021)"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Bobbili DR, Lal D, May P, Reinthaler EM, Jabbari K, Thiele H, et al. Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. Eur J Hum Genet. 2018;26(2):258\u201364.","DOI":"10.1038\/s41431-017-0034-x"}],"container-title":["Journal of Medicine and Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/medandlife.org\/wp-content\/uploads\/JMedLife-14-424.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T04:51:20Z","timestamp":1673499080000},"score":1,"resource":{"primary":{"URL":"https:\/\/medandlife.org\/wp-content\/uploads\/JMedLife-14-424.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["JMedLife-14-424"],"URL":"https:\/\/doi.org\/10.25122\/jml-2021-0147","relation":{},"ISSN":["1844-122X","1844-3117"],"issn-type":[{"type":"print","value":"1844-122X"},{"type":"electronic","value":"1844-3117"}],"subject":[],"published":{"date-parts":[[2021,6]]}}}