Journal of Molecular Neuroscience

, Volume 67, Issue 4, pp 559–563 | Cite as

Late Infantile Metachromatic Leukodystrophy Due to Novel Pathogenic Variants in the PSAP Gene

  • Miriam KolnikovaEmail author
  • Petra Jungova
  • Martina Skopkova
  • Tomas Foltan
  • Daniela Gasperikova
  • Slavomira Mattosova
  • Jan Chandoga


Impairment of saposin B causes rare atypical metachromatic leukodystrophy (MLD). It is encoded (together with saposin A, C, and D) by the PSAP gene. Only ten pathogenic variants were described in the PSAP gene in MLD patients to date. We report on two novel variants in the PSAP gene - c.679_681delAAG in the saposin B encoding exon 6 and c.1268delT in the saposin D encoding exon 11 in a patient with MLD. We discuss the fact, that variants resulting in PSAP null allele can be shared in patients with the deficit of other saposins (A–D) or whole prosaposin. The patient’s phenotype depends then on the nature of the second allele - atypical Gaucher disease in case of saposin A, MLD in case of saposin B, and Krabbe disease in case of saposin C impairing mutations. The clinically most severe prosaposin deficit is caused by the presence of two PSAP null alleles. Thus, the assessment of a variant impact is needed to prevent delayed diagnosis or misdiagnosis in patients with PSAP mutations.


Metachromatic leukodystrophy Saposin B deficiency PSAP gene 



We are grateful to scientists from Laboratory of Genetics Center Bratislava, Slovak Republic and colleagues from the Institute of Inherited Metabolic Disorders Charles University in Prague, Czech Republic.

Contribution Statement

All authors contributed to the study design and reviewed the manuscript critically and approved the final version. M.K., P.J., M.S., and S.M. researched data and wrote the manuscript; T.F. researched data; J.Ch. and D.G. reviewed and edited the manuscript.


This work was supported by APVV-17-0296.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12031_2019_1259_MOESM1_ESM.pdf (223 kb)
ESM 1 (PDF 223 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Miriam Kolnikova
    • 1
    Email author
  • Petra Jungova
    • 2
  • Martina Skopkova
    • 3
  • Tomas Foltan
    • 1
  • Daniela Gasperikova
    • 3
  • Slavomira Mattosova
    • 2
  • Jan Chandoga
    • 2
  1. 1.Department of Pediatric NeurologyComenius University Faculty of Medicine and National Institute of Children’s DiseasesBratislavaSlovakia
  2. 2.Department of Molecular and Biochemical Genetics - Centre of Rare Genetic DiseasesComenius University Faculty of Medicine & University Hospital BratislavaBratislavaSlovakia
  3. 3.Department of Metabolic Disorders, Institute of Experimental Endocrinology, Biomedical Research CenterSlovak Academy of SciencesBratislavaSlovakia

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