scholarly journals Glycosaminoglycan Storage Disorders: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Maria Francisca Coutinho ◽  
Lúcia Lacerda ◽  
Sandra Alves
Keyword(s):  
Central Nervous System ◽  
Molecular Basis ◽  
Clinical Manifestations ◽  
Lysosomal Storage ◽  
Dysostosis Multiplex ◽  
Cell Tissue ◽  
Degrees Of Severity ◽  
Coarse Facies ◽  
Storage Disorders ◽  
Progressive Course

Impaired degradation of glycosaminoglycans (GAGs) with consequent intralysosomal accumulation of undegraded products causes a group of lysosomal storage disorders known as mucopolysaccharidoses (MPSs). Characteristically, MPSs are recognized by increased excretion in urine of partially degraded GAGs which ultimately result in progressive cell, tissue, and organ dysfunction. There are eleven different enzymes involved in the stepwise degradation of GAGs. Deficiencies in each of those enzymes result in seven different MPSs, all sharing a series of clinical features, though in variable degrees. Usually MPS are characterized by a chronic and progressive course, with different degrees of severity. Typical symptoms include organomegaly, dysostosis multiplex, and coarse facies. Central nervous system, hearing, vision, and cardiovascular function may also be affected. Here, we provide an overview of the molecular basis, enzymatic defects, clinical manifestations, and diagnosis of each MPS, focusing also on the available animal models and describing potential perspectives of therapy for each one.

scholarly journals A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Atul Mehta ◽  
Uma Ramaswami ◽  
Joseph Muenzer ◽  
Roberto Giugliani ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Clinical Manifestations ◽  
Lysosomal Storage Disorders ◽  
Expert Committee ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Access Program ◽  
Storage Disorders

Abstract Background Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

Central nervous system therapy for lysosomal storage disorders

2008 ◽  
Vol 24 (3-4) ◽  
pp. E12 ◽  
Author(s):  
Gregory M. Enns ◽  
Stephen L. Huhn
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Dysfunction ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Systemic Involvement ◽  
Enzyme Replacement ◽  
System Therapy ◽  
Central Nervous System Impairment ◽  
Storage Disorders

✓ Most lysosomal storage disorders are characterized by progressive central nervous system impairment, with or without systemic involvement. Affected individuals have an array of symptoms related to brain dysfunction, the most devastating of which is neurodegeneration following a period of normal development. The blood–brain barrier has represented a significant impediment to developing therapeutic approaches to treat brain disease, but novel approaches—including enzyme replacement, small-molecule, gene, and cell-based therapies—have given children afflicted by these conditions and those who care for them hope for the future.

scholarly journals GM1 gangliosidosis: Case report

2010 ◽  
Vol 63 (5-6) ◽  
pp. 427-430
Author(s):  
Slobodan Obradovic ◽  
Olivera Laban ◽  
Zoran Igrutinovic ◽  
Biljana Vuletic ◽  
Ana Vujic ◽  
...  
Keyword(s):  
Case Report ◽  
Clinical Manifestations ◽  
Lysosomal Storage Disorders ◽  
Facial Features ◽  
Lysosomal Storage ◽  
Nasal Bridge ◽  
Gm1 Gangliosidosis ◽  
Decerebrate Rigidity ◽  
Depressed Nasal Bridge ◽  
Storage Disorders

Introduction. Gangliosidoses occur due to inhereted deficiency of human ? - galaktosidase,resulting in the accumulation of glicophyngolipides within the lisosomes. Clinical manifestations of lysosomal storage disorders are remarkably heterogeneous, they can appear at any age and each of them can vary from mild to severe conditions. Case report. We present a patient with an early, infintile type of GM1 gangliosidosis. The facial features were coarse: hypertelorismus, wide nose, depressed nasal bridge with lingual protrusion. From the very first months of life she had severe generalized hypotonic, delayed development and hapatosplenomegaly. Before she died, when she was 13 months old, she had not had any spontaneus movements, she was deaf and blind, dispnoic, with apnoiccrises, with amimic face, but without seizures and decerebrate rigidity, which often accompanies the terminal stage of this illness. Conclusion. The absence of ?-galaktosidase enzyme activaty at the skin fibroblasts confirmed the definitive diagnosis. There has been no successful treatment so far, but increasingly better results of the gene therapy for other lysosomal storage disorders can make us optimistic.

scholarly journals Lysosomal Storage Disorders: Molecular Basis and Therapeutic Approaches

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 964
Author(s):  
Enrico Moro
Keyword(s):  
Intellectual Disabilities ◽  
Molecular Basis ◽  
Clinical Symptoms ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Therapeutic Approaches ◽  
Progressive Muscle Weakness ◽  
Corneal Clouding ◽  
Storage Disorders ◽  
Bone Deformities

Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe intellectual disabilities, cardiac abnormalities, visceromegaly, and bone deformities to slowly progressive muscle weakness, respiratory insufficiency, eye defects (corneal clouding and retinal degeneration), and skin alterations [...]

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