Document Detail

Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient.
MedLine Citation:
PMID:  15944902     Owner:  NLM     Status:  MEDLINE    
An infant presented with multifocal myoclonus and cyanotic hypoxemia immediately after birth, and severe feeding problems, a protein-losing enteropathy, massive ascites and grand-mal epilepsy marked his rapid downhill course, with death at 17 weeks. At 2 weeks, brain MRI revealed grey matter heterotopias in the parieto-occipital regions suggestive of a cortical morphogenetic disorder. In cultured skin fibroblasts, lipid storage and reduced activities of ceramidase, galactosylceramide beta-galactosidase and glucosylceramide beta-glucosidase were evident. Autopsy disclosed generalised lysosomal lipid storage with macrophages and adrenal cortex prominently affected. The pattern of stored lipids in cultured fibroblasts and in dewaxed spleen tissue blocks was compatible with a diagnosis of prosaposin (pSap) deficiency (pSap-d). Neuropathologically, there was a pronounced generalised neurolysosomal storage combined with a severe depletion of cortical neurons and extreme paucity of myelin and oligodendroglia. This pathology, in particular the massive neuronal loss, differed from that in other neurolipidoses and could be explained by the reduced hydrolysis of multiple sphingolipids and the loss of pSap's neurotrophic function. The absence of immunostainable saposins on tissue sections and the presence of a homozygous c.1 A > T mutation in the prosaposin gene confirmed the diagnosis. PSap-d may be an underdiagnosed condition in infants with severe neurological and dystrophic signs starting immediately after birth.
M Elleder; M Jerábková; A Befekadu; M Hrebícek; L Berná; J Ledvinová; H Hůlková; H Rosewich; N Schymik; B C Paton; K Harzer
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropediatrics     Volume:  36     ISSN:  0174-304X     ISO Abbreviation:  Neuropediatrics     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-09     Completed Date:  2005-09-29     Revised Date:  2008-01-16    
Medline Journal Info:
Nlm Unique ID:  8101187     Medline TA:  Neuropediatrics     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  171-80     Citation Subset:  IM    
Institute of Inherited Metabolic Disorders, Charles University, First Faculty of Medicine, Prague, Czech Republic.
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MeSH Terms
Brain / metabolism,  pathology*
Fatal Outcome
Fibroblasts / metabolism,  pathology
Glycolipids / metabolism
Hydrolases / metabolism
Infant, Newborn
Lipid Metabolism, Inborn Errors / genetics,  metabolism,  pathology*
Saposins / deficiency*,  genetics
Sphingolipids / metabolism
Reg. No./Substance:
0/Glycolipids; 0/PSAP protein, human; 0/Saposins; 0/Sphingolipids; EC 3.-/Hydrolases

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