{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:41:47Z","timestamp":1791013307535,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T00:00:00Z","timestamp":1257292800000},"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":[[2009,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Substrate deprivation therapy has been successfully applied in a number of lysosomal storage diseases, such as Gaucher disease. So far only limited experience is available in Sandhoff disease. We initiated substrate deprivation therapy in one male patient, who initially presented at the age of 3.5 years with epilepsy and regression in motor skills and speech development. Juvenile Sandhoff disease was diagnosed on the basis of a decreased hexosaminidase activity in leukocytes and a homozygous <jats:italic>HEXB<\/jats:italic> gene mutation. After the epilepsy was controlled, the clinical course remained stable for years, defined by a mild proximal myopathy and stable mental retardation. At 14 years of age the patient experienced a second episode with progressively worsening general condition with diminishing muscle power and progressive ataxia. Treatment was started with the <jats:italic>N<\/jats:italic>\u2010alkylated imino sugar miglustat, inhibiting the glucosylceramide synthase, an essential enzyme for the synthesis of glycosphingolipids. Diarrhoea was treated with lactose restriction. We performed detailed biochemical investigations, motor and mental development analysis, brain imaging, organ function studies and quality of life score prior to and at different time points after start of the treatment. Two years after the initiation of therapy the patient has a stable neurological picture without further regression in his motor development, ataxia or intelligence. There is a subjective improvement in the fine motor skills and walking up the stairs but no change in the quality of life score. Under treatment with miglustat the clinical course in our patient with Sandhoff disease did not further deteriorate.<\/jats:p>","DOI":"10.1007\/s10545-009-1261-2","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T08:28:32Z","timestamp":1257496112000},"page":"307-311","source":"Crossref","is-referenced-by-count":23,"title":["Substrate deprivation therapy in juvenile Sandhoff disease"],"prefix":"10.1002","volume":"32","author":[{"given":"S. B.","family":"Wortmann","sequence":"first","affiliation":[{"name":"Department of Paediatrics Radboud University Nijmegen Medical Centre PO Box 9101 huispost 833 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Lefeber","sequence":"additional","affiliation":[{"name":"Laboratory of Paediatrics and Neurology Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Dekomien","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Ruhr University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A. A. P.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Neurology Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"Wevers","sequence":"additional","affiliation":[{"name":"Laboratory of Paediatrics and Neurology Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Morava","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Radboud University Nijmegen Medical Centre PO Box 9101 huispost 833 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,4]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000194225.78917.de"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01074.x"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025902113005"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705155"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6388"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.327"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20242"},{"issue":"1","key":"e_1_2_4_9_1","first-page":"130","article-title":"Substrate deprivation therapy in Sandhoff disease, evidence for improvement in nervous function in patients treated with miglustat","volume":"29","author":"Lachmann RH","year":"2006","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.06.005"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.04.013"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70194-1"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5311.428"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399400001484"},{"issue":"1","key":"e_1_2_4_15_1","first-page":"116","article-title":"Gene expression\u2010targeted isoflavone therapy (GET IT) for mucopolysaccharidosis type III (Sanfilippo disease): a pilot clinical trial","volume":"30","author":"W\u00eagrzyn G","year":"2007","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.06.008"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1261-2","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-009-1261-2","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1261-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:18:16Z","timestamp":1694747896000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-009-1261-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,4]]},"references-count":15,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1007\/s10545-009-1261-2"],"URL":"https:\/\/doi.org\/10.1007\/s10545-009-1261-2","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,4]]}}}