Sapa anal skin disease [RAND=1,30] [RAND=5,10] 10
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Sapa anal skin disease



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To our knowledge, this is the first observation that caspase works as an activator of a protease cascade. Kustermann-Kuhn and Mrs. Phenotypically, pSap-d is a relatively uniform disease of the neonate, whereas SapB-d is heterogeneous with a spectrum similar to that in metachromatic leukodystrophy. Previously we purified an active form of caspase from human corneocyte extract and determined its primary structure 4. The Metabolic and molecular bases of inherited diseases.


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A proteomics-based search for molecules interacting with caspase identified prosaposin and epidermal mesotrypsin as candidates. Prosaposin is a precursor of four sphingolipid activator proteins saposins A—D that are essential for lysosomal hydrolysis of sphingolipids. Thus, we hypothesized that caspase and mesotrypsin participate in processing of prosaposin. Because we identified a saposin A sequence as an interactor with these proteases, we prepared a specific antibody to saposin A and focused on saposin A-related physiological reactions. We found that mesotrypsin generated saposins A—D from prosaposin, and mature caspase contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models.
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Prosaposin deficiency pSap-d and saposin B deficiency SapB-d are both lipid storage disorders caused by mutations in the PSAP gene that codes for the 65—70 kDa prosaposin protein, which is the precursor for four sphingolipid activator proteins, saposins A—D. We report on two new patients with PSAP gene defects; one, with pSap-d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB-d, who presented with a metachromatic leukodystrophy-like 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-d 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 PSAP gene. The pSap-d patient was homozygous for a splice-acceptor site mutation two bases upstream of exon
sapa anal skin disease sapa anal skin disease

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