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