{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:01:43Z","timestamp":1783119703877,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR39587\/MED\/12\/851\/2020"],"award-info":[{"award-number":["BT\/PR39587\/MED\/12\/851\/2020"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metachromatic leukodystrophy (MLD) due to Sap\u2010B deficiency is a rare autosomal recessive disorder caused due to biallelic variants in the <jats:italic>PSAP<\/jats:italic> gene. The <jats:italic>PSAP<\/jats:italic> gene encodes a precursor protein prosaposin, which is subsequently cleaved to form four active glycoproteins: Sap\u2010A, Sap\u2010B, Sap\u2010C, and Sap\u2010D. In case of deficiency of the sphingolipid activator protein Sap\u2010B, there is a gradual accumulation of cerebroside\u20103\u2010sulfate in the myelin of the nervous system resulting in progressive demyelination. Only 12 variants have been reported in the <jats:italic>PSAP<\/jats:italic> gene causing Sap\u2010B deficiency to date. Here, we report two cases of MLD due to Sap\u2010B deficiency (late\u2010infantile and adult\u2010onset form) harboring two novel missense variants c.688T\u2009&gt;\u2009G and c.593G\u2009&gt;\u2009A in the <jats:italic>PSAP<\/jats:italic> gene respectively. This study reports the third case of adult\u2010onset MLD due to Sap\u2010B deficiency in the world. The proband, a 3\u2010year\u2010old male child presented with complaints of hypotonia, lower limb tremors and global developmental delay. His MRI showed hyperintense signals in the bilateral cerebellar white matter. Overall, the findings were suggestive of metachromatic leukodystrophy. The second case was a 19\u2010year\u2010old male child with clinical features of regression of speech, gait ataxia and bilateral tremors referred to our clinic. MRI data suggested metachromatic leukodystrophy. Normal enzyme activity of arylsulfatase\u2010A led to a suspicion of saposin B deficiency. For both cases, targeted sequencing was performed. This identified homozygous variant c.688T\u2009&gt;\u2009G (p.Cys230Gly) and c.593G\u2009&gt;\u2009A (p.Cys198Tyr) in exon 6 of the <jats:italic>PSAP<\/jats:italic> gene, respectively.<\/jats:p>","DOI":"10.1002\/jmd2.12374","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T17:28:11Z","timestamp":1686072491000},"page":"265-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Late infantile and adult\u2010onset metachromatic leukodystrophy due to novel missense variants in the <scp><i>PSAP<\/i><\/scp> gene: Case report from India"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5936-5192","authenticated-orcid":false,"given":"Jayesh","family":"Sheth","sequence":"first","affiliation":[{"name":"FRIGE's Institute of Human Genetics, FRIGE House  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2057-5480","authenticated-orcid":false,"given":"Aadhira","family":"Nair","sequence":"additional","affiliation":[{"name":"FRIGE's Institute of Human Genetics, FRIGE House  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riddhi","family":"Bhavsar","sequence":"additional","affiliation":[{"name":"FRIGE's Institute of Human Genetics, FRIGE House  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Shah","sequence":"additional","affiliation":[{"name":"Smt. NHL Municipal Medical College  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Tayade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. Panjabrao Deshmukh Memorial Medical College  Amravati India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ratna","family":"Prabha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science The M. S. 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