Current molecular genetics strategies for the diagnosis of lysosomal storage disorders

Expert Rev Mol Diagn. 2016;16(1):113-23. doi: 10.1586/14737159.2016.1121101. Epub 2015 Dec 9.


Lysosomal storage disorders (LSDs) are a group of almost 50 monogenic diseases characterized by mutations causing deficiency of lysosomal enzymes or non-enzyme proteins involved in transport across the lysosomal membrane, protein maturation or lysosomal biogenesis. Usually, affected patients are normal at birth and have a progressive and severe disease with high morbidity and reduced life expectancy. The overall incidence of LSDs is usually estimated as 1:5000, but newborn screening studies are indicating that it could be much higher. Specific therapies were already developed for selected LSDs, making the timely and correct diagnosis very important for successful treatment and also for genetic counseling. In most LSD cases the biochemical techniques provide a reliable diagnosis. However, the identification of pathogenic mutations by genetic analysis is being increasingly recommended to provide additional information. In this paper we discuss the conventional methods for genetic analysis used in the LSDs [restriction fragment length polymorphism (RFLP), amplification-refractory mutation system (ARMS), single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (dHPLC), real-time polymerase chain reaction, high resolution melting (HRM), multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing] and also the newer approaches [massive parallel sequencing, array comparative genomic hybridization (CGH)].

Keywords: Lysosomal storage diseases; enzyme deficiency; massive parallel sequencing; molecular diagnosis; mutation identification.

Publication types

  • Review

MeSH terms

  • Genetic Counseling
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lysosomal Storage Diseases / diagnosis*
  • Lysosomal Storage Diseases / genetics*
  • Lysosomal Storage Diseases / pathology
  • Mutation
  • Pathology, Molecular / classification
  • Pathology, Molecular / methods*
  • Proteins / genetics*


  • Proteins