{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:51:41Z","timestamp":1783525901239,"version":"3.55.0"},"reference-count":0,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T00:00:00Z","timestamp":1112313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>A multi\u2010approach study in a series of 25 Czech and Slovak patients with acid sphingomyelinase deficiency revealed a broad phenotypic variability within Niemann\u2013Pick disease types A and B. The clinical manifestation of only 9 patients fulfilled the historical classification: 5 with the rapidly progressive neurovisceral infantile type A and 4 with a slowly progressive visceral type B. Sixteen patients (64%) represented a hitherto scarcely documented \u2018intermediate type\u2019 (IT). Twelve patients showed a protracted neurovisceral course with overt or mild neurological symptoms, three a rapidly progressing fatal visceral affection with rudimentary neurological lesion. One patient died early from a severe visceral disease. The genotype in our patients was represented by 4 frameshift and 14 missense mutations. Six were novel (G166R, R228H, A241V, D251E, D278A, A595fsX601). The Q292K mutation (homoallelic, heteroallelic) was strongly associated with a protracted neurovisceral phenotype (10 of 12 cases). The sphingomyelin loading test in living fibroblasts resulted in total degradation from less than 2% in classical type A to 70\u201380% in classical type B. In the IT group it ranged from 5% to 49% in a 24\u2009h chase. The liver storage showed three patterns: diffuse, zonal (centrolobular), and discrete submicroscopic. Our series showed a notable variability in both the neurological and visceral lesions as well as in their proportionality and synchrony, and demonstrates a continuum between the historical \u2018A\u2019 and \u2018B\u2019 phenotypes of ASM deficiency. This points to a broad phenotypic potential of ASM deficiency, suggesting the existence of still unknown factors independently controlling the storage level in the visceral and neuronal compartments. This report highlights the important position of the IT in the ASM deficiency phenotype classification. We define IT as a cluster of variants combining clinical features of both the classical types. The protracted neuronopathic variant with overt, borderline or subclinical neurology prevails and is important in view of future enzyme replacement therapy. It appears more common in central Europe. The visceral, rapidly progressing early fatal type has been recognized rarely so far.<\/jats:p>","DOI":"10.1007\/s10545-005-5671-5","type":"journal-article","created":{"date-parts":[[2005,5,4]],"date-time":"2005-05-04T09:14:17Z","timestamp":1115198057000},"page":"203-227","source":"Crossref","is-referenced-by-count":97,"title":["Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty\u2010five Czech and Slovak patients. A multi\u2010approach study"],"prefix":"10.1002","volume":"28","author":[{"given":"H.","family":"Pavl\u016f\u2010Pereira","sequence":"first","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Asfaw","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Poup\u010dtov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ledvinov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sikora","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Vanier","sequence":"additional","affiliation":[{"name":"INSERM U189, Lyon\u2010Sud Medical School, and Laboratoire Fondation Gillet M\u00e9rieux Lyon\u2010Sud Hospital  Pierre\u2010B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Sandhoff","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry University of Bonn  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Zeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Charles University 1st Faculty of Medicine and University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Novotn\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Chudoba","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Elleder","sequence":"additional","affiliation":[{"name":"Institute of Inherited Metabolic Disorders  Czech Republic"},{"name":"Institute of Inherited Metabolic Disorders  Division B, Bldg. D, Ke Karlovu 2 Prague 2 128 08 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,4]]},"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-005-5671-5","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-005-5671-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T23:24:56Z","timestamp":1694820296000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-005-5671-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,4]]}},"alternative-id":["10.1007\/s10545-005-5671-5"],"URL":"https:\/\/doi.org\/10.1007\/s10545-005-5671-5","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4]]}}}