{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:23:48Z","timestamp":1791685428837,"version":"4.3.4"},"reference-count":147,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Midwest Athletes Against Childhood Cancer, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency disorders caused by ASAH1 gene mutations. Currently, 73 different mutations in the ASAH1 gene have been described in humans. These mutations lead to reduced ACDase activity and ceramide (Cer) accumulation in many tissues. Presenting as divergent clinical phenotypes, the symptoms of FD vary depending on central nervous system (CNS) involvement and severity. Classic signs of FD include, but are not limited to, a hoarse voice, distended joints, and lipogranulomas found subcutaneously and in other tissues. Patients with SMA-PME lack the most prominent clinical signs seen in FD. Instead, they demonstrate muscle weakness, tremors, and myoclonic epilepsy. Several ACDase-deficient mouse models have been developed to help elucidate the complex consequences of Cer accumulation. In this review, we compare clinical reports on FD patients and experimental descriptions of ACDase-deficient mouse models. We also discuss clinical presentations, potential therapeutic strategies, and future directions for the study of FD and SMA-PME.<\/jats:p>","DOI":"10.3390\/biom13020274","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:04:48Z","timestamp":1675227888000},"page":"274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4878-5711","authenticated-orcid":false,"given":"Annie","family":"Kleynerman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-638X","authenticated-orcid":false,"given":"Jitka","family":"Rybova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"McKillop","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Levade","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie M\u00e9tabolique, CHU Toulouse, and INSERM U1037, Centre de Recherches en Canc\u00e9rologie de Toulouse, Universit\u00e9 Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Medin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11098","DOI":"10.1074\/jbc.270.19.11098","article-title":"Purification, characterization, and biosynthesis of human acid ceramidase","volume":"270","author":"Bernardo","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1016\/S0021-9258(18)51879-2","article-title":"Enzymic hydrolysis and synthesis of ceramides","volume":"238","author":"Gatt","year":"1963","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35352","DOI":"10.1074\/jbc.M103066200","article-title":"Human acid ceramidase: Processing, glycosylation, and lysosomal targeting","volume":"276","author":"Ferlinz","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/s41467-018-03844-2","article-title":"Structural basis for the activation of acid ceramidase","volume":"9","author":"Gebai","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"29948","DOI":"10.1074\/jbc.M303310200","article-title":"The reverse activity of human acid ceramidase","volume":"278","author":"Okino","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1006\/geno.1999.5940","article-title":"The human acid ceramidase gene (ASAH): Structure, chromosomal location, mutation analysis, and expression","volume":"62","author":"Li","year":"1999","journal-title":"Genomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"158972","DOI":"10.1016\/j.bbalip.2021.158972","article-title":"Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines","volume":"1866","author":"Tsuboi","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.embor.7400208","article-title":"The complex life of simple sphingolipids","volume":"5","author":"Futerman","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11221","DOI":"10.1038\/s41598-021-90219-1","article-title":"Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin","volume":"11","author":"Lai","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1111\/cas.15123","article-title":"Inhibition of acid ceramidase elicits mitochondrial dysfunction and oxidative stress in pancreatic cancer cells","volume":"112","author":"Taniai","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hawkins, C.C., Jones, A.B., Gordon, E.R., Williford, S.E., Harsh, Y., Ziebro, J.K., Landis, C.J., Gc, S., Crossman, D.K., and Cooper, S.J. (2022). Targeting Acid Ceramidase Inhibits Glioblastoma Cell Migration through Decreased AKT Signaling. Cells, 11.","DOI":"10.3390\/cells11121873"},{"key":"ref_13","first-page":"499","article-title":"A lipid metabolic disorder: Disseminated lipogranulomatosis; a syndrome with similarity to, and important difference from, Niemann-Pick and Hand-Sch\u00fcller-Christian disease","volume":"84","author":"Farber","year":"1952","journal-title":"AMA Am. J. Dis. Child"},{"key":"ref_14","unstructured":"Stanbury, J.B. (1983). Metabolic Basis of Inherited Disease, McGraw-Hill."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13023-018-0845-z","article-title":"Acid ceramidase deficiency: Farber disease and SMA-PME","volume":"13","author":"Yu","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","unstructured":"Levade, T., Sandhoff, K., Schulze, H., and Medin, J.A. (2019). Online Metabolic & Molecular Bases of Inherited Disease (OMMBID), McGraw-Hill."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/cge.13974","article-title":"A case of ASAH1-related pure SMA evolving into adult-onset Farber disease","volume":"100","author":"Puma","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/ajmg.a.61764","article-title":"Spinal muscular atrophy and Farber disease due to ASAH1 variants: A case report","volume":"182","author":"Lee","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1750-1172-6-71","article-title":"Spinal muscular atrophy","volume":"6","author":"Mercuri","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1001\/archneurol.2011.74","article-title":"Spinal muscular atrophy: A timely review","volume":"68","author":"Kolb","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2012.05.001","article-title":"Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1","volume":"91","author":"Zhou","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gowda, V.L., Fernandez-Garcia, M.A., Jungbluth, H., and Wraige, E. (2022). New treatments in spinal muscular atrophy. Arch. Dis. Child.","DOI":"10.1136\/archdischild-2021-323605"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.4103\/0028-3886.68660","article-title":"Progressive myoclonic epilepsy","volume":"58","author":"Satishchandra","year":"2010","journal-title":"Neurol. India"},{"key":"ref_24","first-page":"116","article-title":"Hereditary myoclonus and progressive muscular atrophy: A new syndrome","volume":"103","author":"Jankovic","year":"1978","journal-title":"Trans. Am. Neurol. Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/epi.12977","article-title":"Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH 1","volume":"56","author":"Rubboli","year":"2015","journal-title":"Epilepsia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/cge.12307","article-title":"Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy","volume":"86","author":"Dyment","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_27","unstructured":"Dyment, D.A., Bennett, S.A.L., Medin, J.A., and Levade, T. (1993). ASAH1-Related Disorders, University of Washington."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1684\/epd.2016.0858","article-title":"Spinal muscular atrophy associated with progressive myoclonus epilepsy","volume":"18","author":"Topaloglu","year":"2016","journal-title":"Epileptic Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1055\/s-2002-37087","article-title":"Spinal muscular atrophy with progressive myoclonic epilepsy: Report of new cases and review of the literature","volume":"33","author":"Haliloglu","year":"2002","journal-title":"Neuropediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/acn3.51687","article-title":"The clinical spectrum of SMA-PME and in vitro normalization of its cellular ceramide profile","volume":"9","author":"Lee","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1159\/000341453","article-title":"Construction of conditional acid ceramidase knockout mice and in vivo effects on oocyte development and fertility","volume":"30","author":"Eliyahu","year":"2012","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1006\/geno.2002.6686","article-title":"Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes","volume":"79","author":"Li","year":"2002","journal-title":"Genomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1096\/fj.06-7016com","article-title":"Acid ceramidase is a novel factor required for early embryo survival","volume":"21","author":"Eliyahu","year":"2007","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"881848","DOI":"10.3389\/fmed.2022.881848","article-title":"Targeting acid ceramidase ameliorates fibrosis in mouse models of non-alcoholic steatohepatitis","volume":"9","author":"Yu","year":"2022","journal-title":"Front. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/emmm.201202301","article-title":"Systemic ceramide accumulation leads to severe and varied pathological consequences","volume":"5","author":"Alayoubi","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e162","DOI":"10.3324\/haematol.2014.108530","article-title":"Markedly perturbed hematopoiesis in acid ceramidase deficient mice","volume":"100","author":"Dworski","year":"2015","journal-title":"Haematologica"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.bbadis.2016.11.031","article-title":"Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy","volume":"1863","author":"Dworski","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.ajpath.2016.12.005","article-title":"Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities","volume":"187","author":"Sikora","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"L406","DOI":"10.1152\/ajplung.00223.2017","article-title":"Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency","volume":"314","author":"Yu","year":"2018","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1038\/s41598-018-20052-6","article-title":"Deletion of MCP-1 Impedes Pathogenesis of Acid Ceramidase Deficiency","volume":"8","author":"Yu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ajpath.2018.10.018","article-title":"Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment","volume":"189","author":"Yu","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1038\/s41374-019-0271-4","article-title":"Hepatic pathology and altered gene transcription in a murine model of acid ceramidase deficiency","volume":"99","author":"Yu","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/jimd.12552","article-title":"Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency","volume":"45","author":"Rybova","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1515\/hsz-2018-0170","article-title":"Pathological manifestations of Farber disease in a new mouse model","volume":"399","author":"Beckmann","year":"2018","journal-title":"Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Beckmann, N., Becker, K.A., Kadow, S., Schumacher, F., Kramer, M., K\u00fchn, C., Schulz-Schaeffer, W.J., Edwards, M.J., Kleuser, B., and Gulbins, E. (2019). Acid Sphingomyelinase Deficiency Ameliorates Farber Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246253"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"158532","DOI":"10.1016\/j.bbalip.2019.158532","article-title":"Endothelial acid ceramidase in exosome-mediated release of NLRP3 inflammasome products during hyperglycemia: Evidence from endothelium-specific deletion of Asah1 gene","volume":"1864","author":"Yuan","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fcell.2020.00111","article-title":"Downregulation of Lysosomal Acid Ceramidase Mediates HMGB1-Induced Migration and Proliferation of Mouse Coronary Arterial Myocytes","volume":"8","author":"Yuan","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.ajpath.2020.02.008","article-title":"Podocytopathy and Nephrotic Syndrome in Mice with Podocyte-Specific Deletion of the Asah1 Gene: Role of Ceramide Accumulation in Glomeruli","volume":"190","author":"Li","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1096\/fj.201700585R","article-title":"Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment","volume":"32","author":"Espaillat","year":"2018","journal-title":"FASEB J."},{"key":"ref_50","first-page":"816","article-title":"Lipogranulomatosis; a new lipo-glycoprotein storage disease","volume":"24","author":"Farber","year":"1957","journal-title":"J. Mt. Sinai Hosp. NY"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0887-8994(86)90082-2","article-title":"Farber lipogranulomatosis: An unusual presentation in a black child","volume":"2","author":"Eviatar","year":"1986","journal-title":"Pediatr. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0002-9343(69)90202-2","article-title":"Farber\u2019s lipogranulomatosis. Report of a case and demonstration of an excess of free ceramide and ganglioside","volume":"47","author":"Moser","year":"1969","journal-title":"Am. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/BF00714300","article-title":"Farber disease with prolonged survival","volume":"16","author":"Fiumara","year":"1993","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3346\/jkms.1998.13.1.95","article-title":"A case of Farber lipogranulomatosis","volume":"13","author":"Kim","year":"1998","journal-title":"J. Korean Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/00005176-200302000-00021","article-title":"Farber disease diagnosed after liver transplantation","volume":"36","author":"Salo","year":"2003","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ejpn.2010.06.002","article-title":"Farber lipogranulomatosis type 1\u2014Late presentation and early death in a Croatian boy with a novel homozygous ASAH1 mutation","volume":"15","author":"Sabourdy","year":"2011","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3109\/00365517109080235","article-title":"Ceramides in a patient with lipogranulomatosis (Farber\u2019s disease) with chronic course","volume":"27","author":"Samuelsson","year":"1971","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF00685981","article-title":"Farber\u2019s disease in two siblings, sural nerve and subcutaneous biopsies by light and electron microscopy","volume":"72","author":"Pellissier","year":"1986","journal-title":"Acta Neuropathol."},{"key":"ref_59","first-page":"521","article-title":"Farber disease: Report of three cases with joint involvement mimicking juvenile idiopathic arthritis","volume":"19","author":"Moghadam","year":"2019","journal-title":"J. Musculoskelet. Neuronal. Interact."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S0022-3476(84)81106-3","article-title":"Phenotypic variability in siblings with Farber disease","volume":"104","author":"Antonarakis","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/art.1780090407","article-title":"A disorder of mucopolysaccharide metabolism with articular, respiratory, and neurologic manifestations","volume":"9","author":"Bierman","year":"1966","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.nmd.2015.09.007","article-title":"Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy","volume":"25","author":"Gan","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1440-1827.1979.tb01298.x","article-title":"Farber\u2019s Disease (Disseminated Lipogranulomatosis)\u2014A Pathological, Histochemical and Ultrastructural Study\u2014","volume":"29","author":"Tanaka","year":"1979","journal-title":"Pathol. Int."},{"key":"ref_64","first-page":"221","article-title":"Farber\u2019s disease. Report of a case with observations on its histogenesis and notes on the nature of the stored material","volume":"61","author":"Martz","year":"1962","journal-title":"J. Pediatr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/cge.13834","article-title":"ASAH1-related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype","volume":"98","author":"Mahmoud","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3109\/01913128709048433","article-title":"Farber\u2019s disease: A fine structural study","volume":"11","author":"Abenoza","year":"1987","journal-title":"Ultrastruct. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2350\/07-08-0318.1","article-title":"Farber\u2019s disease type IV presenting with cholestasis and neonatal liver failure: Report of two cases","volume":"11","author":"Willis","year":"2008","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/BF01799842","article-title":"Bone marrow involvement and obstructive jaundice in Farber lipogranulomatosis: Clinical and autopsy report of a new case","volume":"19","author":"Nowaczyk","year":"1996","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eaay8798","DOI":"10.1126\/scitranslmed.aay8798","article-title":"Targeting acid ceramidase inhibits YAP\/TAZ signaling to reduce fibrosis in mice","volume":"12","author":"Alsamman","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/nm.3282","article-title":"Targeting of \u03b1v integrin identifies a core molecular pathway that regulates fibrosis in several organs","volume":"19","author":"Henderson","year":"2013","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1546-0096-5-15","article-title":"Farber disease: Clinical presentation, pathogenesis and a new approach to treatment","volume":"5","author":"Ehlert","year":"2007","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1038\/ejhg.2016.28","article-title":"ASAH1 variant causing a mild SMA phenotype with no myoclonic epilepsy: A clinical, biochemical and molecular study","volume":"24","author":"Filosto","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s004310050603","article-title":"Hydrops fetalis: Manifestation in lysosomal storage diseases including Farber disease","volume":"156","author":"Kattner","year":"1997","journal-title":"Eur. J. Pediatr."},{"key":"ref_74","first-page":"206A","article-title":"Farber\u2019s lipogranulomatosis: Variability of expression and clinical overlap with histiocytosis","volume":"17","author":"Antonarakis","year":"1983","journal-title":"Pediatr. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s100240010107","article-title":"Intrauterine fetal death due to Farber disease: Case report","volume":"3","author":"Groener","year":"2000","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/bjh.14265","article-title":"Early morphological diagnosis of Farber disease","volume":"175","author":"Nivaggioni","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1442-200X.1992.tb00928.x","article-title":"A case of Farber disease","volume":"34","author":"Fujiwaki","year":"1992","journal-title":"Acta Paediatr. JPN"},{"key":"ref_78","first-page":"175","article-title":"Disseminated lipogranulomatosis","volume":"46","author":"Mondal","year":"2009","journal-title":"Indian Pediatr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/jimd.12043","article-title":"Allogeneic hematopoietic cell transplantation in Farber disease","volume":"42","author":"Ehlert","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s10545-012-9573-z","article-title":"Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis","volume":"36","author":"Kostik","year":"2013","journal-title":"J Inherit. Metab. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s004310050867","article-title":"An 18-month-old girl with hoarseness, stiff joints and subcutaneous nodules","volume":"157","author":"Klingkowski","year":"1998","journal-title":"Eur. J. Pediatr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1148\/82.4.675","article-title":"Disseminated lipogranulomatosis: Early roentgenographic changes","volume":"82","author":"Schanche","year":"1964","journal-title":"Radiology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1093\/rheumatology\/keu010","article-title":"Farber disease in infancy resembling juvenile idiopathic arthritis: Identification of two new mutations and a good early response to allogeneic haematopoietic stem cell transplantation","volume":"53","author":"Torcoletti","year":"2014","journal-title":"Rheumatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.braindev.2011.07.003","article-title":"Novel V97G ASAH1 mutation found in Farber disease patients: Unique appearance of the disease with an intermediate severity, and marked early involvement of central and peripheral nervous system","volume":"34","author":"Chedrawi","year":"2012","journal-title":"Brain Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/BF01600282","article-title":"Farber disease: An ultrastructural study","volume":"420","author":"Dumontel","year":"1992","journal-title":"Virchows Archiv. A"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e240742","DOI":"10.1136\/bcr-2020-240742","article-title":"Novel manifestations of Farber disease mimicking neuronopathic Gaucher disease","volume":"14","author":"Mhatre","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/BF02531715","article-title":"Fatty acid composition of free ceramides of kidney and cerebellum from a patient with Farber\u2019s disease","volume":"8","author":"Sugita","year":"1973","journal-title":"Lipids"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0022-2275(20)36799-7","article-title":"High performance liquid chromatography of ceramides: Application to analysis in human tissues and demonstration of ceramide excess in Farber\u2019s disease","volume":"15","author":"Sugita","year":"1974","journal-title":"J. Lipid Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.29245\/2572-9411\/2020\/2.1197","article-title":"Farber disease: A Fatal Childhood Disorder with Nervous System Involvement","volume":"5","author":"Kraoua","year":"2020","journal-title":"J. Rare Dis. Res. Treat."},{"key":"ref_90","first-page":"320","article-title":"Novel biochemical abnormalities and genotype in Farber disease","volume":"49","author":"Muranjan","year":"2012","journal-title":"Indian Pediatr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2217\/fnl.13.58","article-title":"Neurodegeneration in spinal muscular atrophy: From disease phenotype and animal models to therapeutic strategies and beyond","volume":"9","author":"Monani","year":"2014","journal-title":"Future Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jpeds.2003.09.051","article-title":"Successful hematopoietic stem cell transplantation in Farber disease","volume":"144","author":"Vormoor","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ymgme.2008.08.003","article-title":"In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease","volume":"95","author":"Ramsubir","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.stem.2017.10.010","article-title":"Hematopoietic stem cell gene therapy: Progress and lessons learned","volume":"21","author":"Morgan","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.1365-2133.1989.tb08222.x","article-title":"Farber\u2019s lipogranulomatosis in siblings: Light and electron microscopic studies","volume":"121","author":"Chanoki","year":"1989","journal-title":"Br. J. Dermatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/00000372-198000220-00011","article-title":"Subtle clues to diagnosis of skin diseases by electron microscopy:\u201cFarber bodies\u201d in disseminated lipogranulomatosis (Farber\u2019s disease)","volume":"2","author":"Schmoeckel","year":"1980","journal-title":"Am. J. Dermatopathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/cge.12316","article-title":"Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: Analyses of exonic splicing enhancer inactivating mutation","volume":"86","author":"Bashyam","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1046\/j.1365-2133.1999.02986.x","article-title":"Lipoid proteinosis. A biochemical and ultrastructural investigation of two new cases","volume":"141","author":"Navarro","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_99","first-page":"97","article-title":"Farber disease overlapping with stiff skin syndrome: Expanding the spectrum","volume":"10","author":"Katoury","year":"2009","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/ajmg.a.61752","article-title":"Farber disease in a patient from China","volume":"182","author":"Bao","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/ejhg.2017.121","article-title":"Identification of ASAH1 as a susceptibility gene for familial keloids","volume":"25","author":"Hu","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1001\/archopht.1966.00970050754007","article-title":"Retinopathy in a case of Farber\u2019s lipogranulomatosis","volume":"75","author":"Cogan","year":"1966","journal-title":"Arch. Ophthalmol."},{"key":"ref_103","first-page":"502","article-title":"Farber\u2019s disease","volume":"39","author":"Chandwani","year":"2002","journal-title":"Indian Pediatr."},{"key":"ref_104","first-page":"227","article-title":"Farber Lipogranulomatosis: A Report of a Case with Nystagmus, Myoclonus and Convulsions","volume":"9","author":"Ohfu","year":"1987","journal-title":"Brain Dev."},{"key":"ref_105","first-page":"42","article-title":"An autopsy case of Farber\u2019s lipogranulomatosis in a Japanese boy with gastrointestinal involvement","volume":"42","author":"Koga","year":"1992","journal-title":"Acta Pathol. JPN"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/002215540004800106","article-title":"Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease","volume":"48","author":"Farina","year":"2000","journal-title":"J. Histochem. Cytochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1080\/21678707.2017.1359086","article-title":"Morbidity and mortality associated with Farber disease and prospects for therapy","volume":"5","author":"Schuchman","year":"2017","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/j.ymgme.2015.12.364","article-title":"Farber disease: Implications of anti-inflammatory treatment","volume":"2","author":"Mitchell","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1006\/geno.1998.5334","article-title":"Cloning and characterization of the full-length cDNA and genomic sequences encoding murine acid ceramidase","volume":"50","author":"Li","year":"1998","journal-title":"Genomics"},{"key":"ref_110","first-page":"2555235","article-title":"Farber Disease Mimicking Juvenile Idiopathic Arthritis: The First Reported Case in Qatar and Review of the Literature","volume":"2022","author":"Toma","year":"2022","journal-title":"Case Rep. Genet."},{"key":"ref_111","first-page":"54","article-title":"A case report of childhood Farber\u2019s disease and literature review","volume":"55","author":"Bao","year":"2017","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1002\/art.39659","article-title":"Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber\u2019s Disease","volume":"68","author":"Kariminejad","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s00431-013-2098-0","article-title":"Odontoid infiltration and spinal compression in Farber Disease: Reversal by haematopoietic stem cell transplantation","volume":"173","author":"Jarisch","year":"2014","journal-title":"Eur. J. Pediatr."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"El-Darouti, M.A. (2013). Challenging Cases in Dermatology, Springer.","DOI":"10.1007\/978-1-4471-4249-2"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/00000637-199710000-00011","article-title":"First case of surgical treatment of Farber\u2019s disease","volume":"39","author":"Haraoka","year":"1997","journal-title":"Ann. Plast. Surg."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1053\/jhsu.2002.32618","article-title":"Surgical treatment of hand disorders in Farber\u2019s disease: A case report","volume":"27","author":"Moritomo","year":"2002","journal-title":"J. Hand Surg."},{"key":"ref_117","first-page":"137","article-title":"Outcome of displacement bone marrow transplantation in Farber\u2019s disease: A report of a case","volume":"1989","author":"Souillet","year":"1989","journal-title":"Correct. Certain. Genet. Dis. Transplantation. Lond. Cogent"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/sj.bmt.1702489","article-title":"Bone marrow transplantation for infantile ceramidase deficiency (Farber disease)","volume":"26","author":"Yeager","year":"2000","journal-title":"Bone Marrow Transpl."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.seizure.2016.09.007","article-title":"Eyelid myoclonic status epilepticus: A rare phenotype in spinal muscular atrophy with progressive myoclonic epilepsy associated with ASAH1 gene mutation","volume":"42","author":"Tekturk","year":"2016","journal-title":"Seizure Eur. J. Epilepsy"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"424","DOI":"10.25122\/jml-2021-0147","article-title":"Clinical features and genetics in non-5q spinal muscular atrophy caused by acid ceramidase deficiency","volume":"14","author":"Axente","year":"2021","journal-title":"J. Med. Life"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/2042018810384429","article-title":"Therapeutic approaches for lysosomal storage diseases","volume":"1","author":"Pastores","year":"2010","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S104","DOI":"10.1016\/j.ymgme.2014.12.236","article-title":"Novel use of the lysosomal enzyme acid ceramidase for the treatment of inflammatory lung diseases, including cystic fibrosis","volume":"114","author":"Schuchman","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bbacli.2017.02.001","article-title":"Enzyme replacement therapy for Farber disease: Proof-of-concept studies in cells and mice","volume":"7","author":"He","year":"2017","journal-title":"BBA Clin."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"559804","DOI":"10.3389\/fmolb.2020.559804","article-title":"CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges","volume":"7","author":"Edelmann","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1021\/acs.molpharmaceut.6b00037","article-title":"Insulin Receptor Antibody\u2212\u03b1-N-Acetylglucosaminidase Fusion Protein Penetrates the Primate Blood\u2013Brain Barrier and Reduces Glycosoaminoglycans in Sanfilippo Type B Fibroblasts","volume":"13","author":"Boado","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1517\/14728220903357512","article-title":"Acid ceramidase upregulation in prostate cancer: Role in tumor development and implications for therapy","volume":"13","author":"Liu","year":"2009","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Lai, M., La Rocca, V., Amato, R., Freer, G., Costa, M., Spezia, P.G., Quaranta, P., Lombardo, G., Piomelli, D., and Pistello, M. (2021). Ablation of Acid Ceramidase Impairs Autophagy and Mitochondria Activity in Melanoma Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063247"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Clifford, R.E., Govindarajah, N., Bowden, D., Sutton, P., Glenn, M., Darvish-Damavandi, M., Buczacki, S., McDermott, U., Szulc, Z., and Ogretmen, B. (2020). Targeting Acid Ceramidase to Improve the Radiosensitivity of Rectal Cancer. Cells, 9.","DOI":"10.3390\/cells9122693"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"83208","DOI":"10.18632\/oncotarget.13079","article-title":"Acid ceramidase is upregulated in AML and represents a novel therapeutic target","volume":"7","author":"Tan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/mt.2015.62","article-title":"Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders","volume":"23","author":"Parenti","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/s41467-021-21371-5","article-title":"Lentivirus-mediated gene therapy for Fabry disease","volume":"12","author":"Khan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0140-6736(21)02017-1","article-title":"Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: Long-term results from a non-randomised, open-label, phase 1\/2 trial and expanded access","volume":"399","author":"Fumagalli","year":"2022","journal-title":"Lancet"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1089\/10430349950018003","article-title":"Retrovirus-mediated correction of the metabolic defect in cultured Farber disease cells","volume":"10","author":"Medin","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1089\/hum.2010.195","article-title":"Autologous transplantation of lentivector\/acid ceramidase-transduced hematopoietic cells in nonhuman primates","volume":"22","author":"Walia","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Zhang, H., Nagree, M.S., Liu, H., Pan, X., Medin, J.A., and Lipinski, D.M. (2022). rAAV-mediated over-expression of acid ceramidase prevents retinopathy in a mouse model of Farber lipogranulomatosis. Gene Ther.","DOI":"10.1038\/s41434-022-00359-w"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1001\/jamaneurol.2021.1272","article-title":"Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy","volume":"78","author":"Mendell","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"S208","DOI":"10.1016\/j.nmd.2017.06.412","article-title":"AVXS-101 phase 1 gene therapy clinical trial in SMA type 1: End-of-study event free survival and achievement of developmental milestones","volume":"27","author":"Mendell","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7411","DOI":"10.1038\/s41598-017-07606-w","article-title":"Complete Acid Ceramidase ablation prevents cancer-initiating cell formation in melanoma cells","volume":"7","author":"Lai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1021\/acs.jmedchem.8b01723","article-title":"Molecular Mechanism of Inhibition of Acid Ceramidase by Carmofur","volume":"62","author":"Dementiev","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.bbadis.2016.05.001","article-title":"Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy","volume":"1862","author":"Schuchman","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e00677","DOI":"10.1128\/IAI.00677-20","article-title":"Acid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections","volume":"89","author":"Becker","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1465-9921-14-96","article-title":"Ceramides: A potential therapeutic target in pulmonary emphysema","volume":"14","author":"Tibboel","year":"2013","journal-title":"Respir. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.freeradbiomed.2018.11.023","article-title":"Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis","volume":"131","author":"Bodas","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.chom.2017.05.001","article-title":"\u03b21-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections","volume":"21","author":"Henry","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1164\/rccm.202001-0180OC","article-title":"Recombinant Acid Ceramidase Reduces Inflammation and Infection in Cystic Fibrosis","volume":"202","author":"Gardner","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"102387","DOI":"10.1016\/j.scr.2021.102387","article-title":"Generation of an induced pluripotent stem cell line (TRNDi030-A) from a patient with Farber disease carrying a homozygous p. Y36C (c. 107 A>G) mutation in ASAH1","volume":"53","author":"Brooks","year":"2021","journal-title":"Stem Cell Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/2\/274\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:20:59Z","timestamp":1760120459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/2\/274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":147,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["biom13020274"],"URL":"https:\/\/doi.org\/10.3390\/biom13020274","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]}}}