Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient
Language English Country Germany Media print
Document type Case Reports, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15944902
DOI
10.1055/s-2005-865608
Knihovny.cz E-resources
- MeSH
- Fatal Outcome MeSH
- Fibroblasts metabolism pathology MeSH
- Glycolipids metabolism MeSH
- Hydrolases metabolism MeSH
- Humans MeSH
- Brain metabolism pathology MeSH
- Infant, Newborn MeSH
- Saposins deficiency genetics MeSH
- Sphingolipids metabolism MeSH
- Lipid Metabolism, Inborn Errors genetics metabolism pathology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glycolipids MeSH
- Hydrolases MeSH
- PSAP protein, human MeSH Browser
- Saposins MeSH
- Sphingolipids MeSH
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.
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