Lysosomal storage diseases
Abstract
Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect 1 in 5,000 live births. LSDs typically present in infancy and childhood, although adult-onset forms also occur. Most LSDs have a progressive neurodegenerative clinical course, although symptoms in other organ systems are frequent. LSD-associated genes encode different lysosomal proteins, including lysosomal enzymes and lysosomal membrane proteins. The lysosome is the key cellular hub for macromolecule catabolism, recycling and signalling, and defects that impair any of these functions cause the accumulation of undigested or partially digested macromolecules in lysosomes (that is, 'storage') or impair the transport of molecules, which can result in cellular damage. Consequently, the cellular pathogenesis of these diseases is complex and is currently incompletely understood. Several LSDs can be treated with approved, disease-specific therapies that are mostly based on enzyme replacement. However, small-molecule therapies, including substrate reduction and chaperone therapies, have also been developed and are approved for some LSDs, whereas gene therapy and genome editing are at advanced preclinical stages and, for a few disorders, have already progressed to the clinic.
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As the prevalence of LSDs increases with newborn screening, new therapeutic interventions such as gene replacement will become critical in addressing all manifestations of LSDs.
“As the prevalence of these disorders increases with the advent of newborn screening, new therapeutic interventions, such as gene replacement, will become critical in addressing all manifestations of LSDs.230,233,234”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [230]
LSDs are a group of inherited metabolic disorders characterized by accumulation of macromolecules inside lysosomes.
“LSDs are a group of inherited metabolic disorders that are characterized by the accumulation of macromolecules inside lysosomes.”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [230]
Collectively, LSDs are relatively common disorders (1:5,000 to 1:5,500), although individually rare.
“Collectively, LSDs are relatively common disorders (1:5,000 to 1:5,500), although individually rare.229, 230, 231”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [230]
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Self-citation
- Authors
- Platt, F. M., d’Azzo, A., Davidson, B. L., Neufeld, E. F., & Tifft, C. J.
- Affiliations
- University of Oxford (GB)
- St. Jude Children's Research Hospital (US)
- Children's Hospital of Philadelphia (US)
- University of California, Los Angeles (US)
- National Institutes of Health (US)
- Corresponding author
- Platt, Frances M.
- Venue
- Nature Reviews Disease Primers
- Published
- 2018-10-01
- Volume
- 4
- Issue
- 1
- ISSN
- 2056-676X (ISSN-L)
- OpenAlex
- W2929961692
- Cited by
- 1,052
- References
- 11
- Citations by year
- 2026: 106 · 2025: 172 · 2024: 190 · 2023: 168 · 2022: 141 · 2021: 130 · 2020: 103 · 2019: 41 · 2018: 1
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Update notices
- Open access
- closed
- Licence
- Locations
- Nature Reviews Disease Primers (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- lysosomal storage disease, lysosomal dysfunction, lysosomal enzymes, lysosomal membrane proteins, autosomal recessive inheritance, neurodegeneration, lysosomal storage, pathogenesis, enzyme replacement therapy, substrate reduction therapy, chaperone therapy, gene therapy, genome editing, diagnosis, therapeutic target
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