The Second Case of Saposin A Deficiency and Altered Autophagy

  • Melis KoseEmail author
  • Secil Akyildiz Demir
  • Gulcin Akinci
  • Cenk Eraslan
  • Unsal Yilmaz
  • Serdar Ceylaner
  • Eser Sozmen Yildirim
  • Volkan Seyrantepe
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)


Krabbe disease is a lysosomal storage disease caused by galactosylceramidase deficiency, resulting in neurodegeneration with a rapid clinical downhill course within the first months of life in the classic infantile form. This process may be triggered by the accumulation of galactosylceramide (GalCer) in nervous tissues. Both the enzyme galactosylceramidase and its in vivo activator molecule, saposin A, are essential during GalCer degradation. A clinical manifestation almost identical to Krabbe disease is observed when, instead of the galactosylceramidase protein, the saposin A molecule is defective. Saposin A results from posttranslational processing of the precursor molecule, prosaposin, encoded by the PSAP gene. Clinical and neuroimaging findings in a 7-month-old child strongly suggested Krabbe disease, but this condition was excluded by enzymatic and genetic testing. However, at whole exome sequencing, the previously undescribed homozygous, obviously pathogenic PSAP gene NM_002778.3:c.209T>G(p.Val70Gly) variant was determined in the saposin A domain of the PSAP gene. Fibroblast studies showed GalCer accumulation and the activation of autophagy for the first time in a case of human saposin A deficiency. Our patient represents the second known case in the literature and provides new information concerning the pathophysiology of saposin A deficiency and its intralysosomal effects.



We thank Centogene AG for whole exome sequencing analyses.


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Melis Kose
    • 1
    Email author
  • Secil Akyildiz Demir
    • 2
  • Gulcin Akinci
    • 3
  • Cenk Eraslan
    • 4
  • Unsal Yilmaz
    • 3
  • Serdar Ceylaner
    • 5
  • Eser Sozmen Yildirim
    • 6
  • Volkan Seyrantepe
    • 2
  1. 1.Pediatric Metabolism DepartmentBehçet Uz Children Research and Training HospitalIzmirTurkey
  2. 2.Molecular Biology and GeneticsIzmir Institute of TechnologyIzmirTurkey
  3. 3.Pediatric Neurology DepartmentBehçet Uz Children Research and Training HospitalIzmirTurkey
  4. 4.Neuroradiology DepartmentEge University Faculty of MedicineIzmirTurkey
  5. 5.Intergen Genetic Diagnosis CentreAnkaraTurkey
  6. 6.Clinical ChemistryEge University Faculty of MedicineIzmirTurkey

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