{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:21:49Z","timestamp":1790043709259,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T00:00:00Z","timestamp":1236297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prosaposin deficiency (pSap\u2010d) and saposin B deficiency (SapB\u2010d) are both lipid storage disorders caused by mutations in the <jats:italic>PSAP<\/jats:italic> gene that codes for the 65\u201370 kDa prosaposin protein, which is the precursor for four sphingolipid activator proteins, saposins A\u2013D. We report on two new patients with <jats:italic>PSAP<\/jats:italic> gene defects; one, with pSap\u2010d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB\u2010d, who presented with a metachromatic leukodystrophy\u2010like disorder but had normal arylsulfatase activity. Screening for urinary sphingolipids was crucial to the diagnosis of both patients, with electrospray ionization tandem mass spectrometry also providing quantification. The pSap\u2010d patient is the first case with this condition where urinary sphingolipids have been investigated. Multiple sphingolipids were elevated, with globotriaosylceramide showing the greatest increase. Both patients had novel mutations in the <jats:italic>PSAP<\/jats:italic> gene. The pSap\u2010d patient was homozygous for a splice\u2010acceptor site mutation two bases upstream of exon 10. This mutation led to a premature stop codon and yielded low levels of transcript. The SapB\u2010d patient was a compound heterozygote with a splice\u2010acceptor site variant exclusively affecting the SapB domain on one allele, and a 2 bp deletion leading to a null, that is, pSap\u2010d mutation, on the other allele. Phenotypically, pSap\u2010d is a relatively uniform disease of the neonate, whereas SapB\u2010d is heterogeneous with a spectrum similar to that in metachromatic leukodystrophy. The possible existence of genotypes and phenotypes intermediate between those of pSap\u2010d and the single saposin deficiencies is speculated. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32712","type":"journal-article","created":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T22:29:58Z","timestamp":1236378598000},"page":"613-621","source":"Crossref","is-referenced-by-count":78,"title":["Prosaposin deficiency and saposin B deficiency (activator\u2010deficient metachromatic leukodystrophy): Report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene 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