Inherited metabolic diseases

2013 ◽  
pp. 1451-1456
Author(s):  
Bernhard Manger
Keyword(s):  
Metabolic Diseases ◽  
Signs And Symptoms ◽  
Lysosomal Storage Diseases ◽  
Organ Damage ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Enzyme Replacement ◽  
Hereditary Disorders ◽  
Enzymatic Pathways

A variety of hereditary disorders can present with structural or functional alterations of the musculoskeletal system. In particular, genetic defects within enzymatic pathways involved in the lysosomal degradation of various substrates can manifest with bone or joint symptoms. Because musculoskeletal complaints are frequently the first reason for the patient to seek medical advice, the rheumatologist may play a crucial role in the early diagnosis of these diseases. Lysosomal storage diseases are a heterogeneous group of individually very rare disorders, but taken together they have a prevalence of more than 1 in 8000 live births. Some of these lysosomal storage diseases can nowadays be treated very effectively by enzyme replacement therapies; however, a timely start of treatment is essential to avoid irreversible organ damage and deterioration of the quality of life. Therefore, the rheumatologist should be able to recognize signs and symptoms of the most frequent treatable lysosomal storage diseases.

scholarly journals Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction

2016 ◽  
Vol 117 (2) ◽  
pp. 66-83 ◽  
Author(s):  
Priya S. Kishnani ◽  
Patricia I. Dickson ◽  
Laurie Muldowney ◽  
Jessica J. Lee ◽  
Amy Rosenberg ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Immune Tolerance Induction ◽  
Storage Diseases ◽  
Enzyme Replacement

Enzyme Replacement Therapy for Genetic Disorders Associated with Enzyme Deficiency

2021 ◽  
Vol 28 ◽  
Author(s):  
Marialaura Marchetti ◽  
Serena Faggiano ◽  
Andrea Mozzarelli
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Rare Diseases ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Genetic Disorders ◽  
Life Quality ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Enzyme Replacement

: Mutations in human genes might lead to loss of functional proteins, causing diseases. Among these genetic disorders, a large class is associated with the deficiency in metabolic enzymes, resulting in both an increase in the concentration of substrates and a loss in the metabolites produced by the catalyzed reactions. The identification of therapeutic actions based on small molecules represents a challenge to medicinal chemists because the target is missing. Alternative approaches are biology-based, ranging from gene and stem cell therapy, CRISPR/Cas9 technology, distinct types of RNAs, and enzyme replacement therapy (ERT). This review will focus on the latter approach that since the 1990s has been successfully applied to cure many rare diseases, most of them being lysosomal storage diseases or metabolic diseases. So far, a dozen enzymes have been approved by FDA/EMA for lysosome storage disorders and only a few for metabolic diseases. Enzymes for replacement therapy are mainly produced in mammalian cells and some in plant cells and yeasts and are further processed to obtain active, highly bioavailable, less degradable products. Issues still under investigation for the increase in ERT efficacy are the optimization of enzymes interaction with cell membrane and internalization, the reduction in immunogenicity, and the overcoming of blood-brain barrier limitations when neuronal cells need to be targeted. Overall, ERT has demonstrated its efficacy and safety in the treatment of many genetic rare diseases, both saving newborn lives and improving patients’ life quality, and represents a very successful example of targeted biologics.

Management of hypersensitivity reactions to enzyme replacement therapy in children with lysosomal storage diseases

2020 ◽  
Vol 125 (4) ◽  
pp. 460-467
Author(s):  
Irem Turgay Yagmur ◽  
Ozlem Unal Uzun ◽  
Aynur Kucukcongar Yavas ◽  
Ilknur Kulhas Celik ◽  
Muge Toyran ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Diseases ◽  
Hypersensitivity Reactions ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Enzyme Replacement

Home-based service for enzyme replacement therapy in lysosomal storage disorders: patient reported outcomes

2018 ◽  
Vol 6 (4) ◽  
pp. 669
Author(s):  
Paolo Tirelli ◽  
Fiorina Giona ◽  
Maja Di Rocco ◽  
Elena Cassinerio ◽  
Antonio Pisani ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Nursing Service ◽  
Enzyme Replacement ◽  
Home Based ◽  
Patient Reported

Background:  Lysosomal storage diseases (LSDs) are a heterogeneous group of rare chronic genetic conditions. The standard-of-care treatment for LSDs is hospital-based infusion of enzyme replacement therapy (ERT), however, over time this can be stressful and inconvenient. The Italian TuTor program, established in 2011 by Sanofi Genzyme, is a professional nursing service providing home-based ERT to patients with LSDs.Objectives:  The current questionnaire-based study was conducted to investigate the level of patient satisfaction with theTuTor program and to shed light on disease perception.Methods:  Patients were enrolled in the TuTor program from 2011 onwards. The first 100 patients enrolled were interviewed at baseline with follow-up interviews conducted at 6, 12 and 18 months.Results: Overall, 52 patients were female; 46 had Gaucher’s disease, 46 had Fabry disease and 8 had mucopolysaccharidosis type 1. Patients took on average >2 hours to receive hospital-based ERT, plus time associated with the infusion; 2 out of 3 patients needed a caregiver to travel to the hospital. After receiving home-based ERT for 6 months, 37% of patients considered their quality of life ‘greatly improved’ (60% at 18 months). Overall, 99% to 100% of patients rated the home-based nursing service as ‘positive’ or ‘very positive’ and reported that they would recommend the service to other patients with their condition.Conclusions: For patients with LSDs eligible for ERT, a disease-specific home-based nursing service increased their perception of quality of life over a hospital-based service and was advantageous in terms of their time and expenditure.

scholarly journals Lysosomal Leukodystrophies Lysosomal Storage Diseases Associated With White Matter Abnormalities

2019 ◽  
Vol 34 (6) ◽  
pp. 339-358 ◽  
Author(s):  
Gustavo H.B. Maegawa
Keyword(s):  
White Matter ◽  
Metabolic Diseases ◽  
Age Groups ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Abnormal Development ◽  
Neurologic Manifestations ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Extrapyramidal Signs

The leukodystrophies are a group of genetic metabolic diseases characterized by an abnormal development or progressive degeneration of the myelin sheath. The myelin is a complex sheath composed of several macromolecules covering axons as an insulator. Each of the leukodystrophies is caused by mutations in genes encoding enzymes that are involved in myelin production and maintenance. The lysosomal storage diseases are inborn disorders of compartmentalized cellular organelles with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes and related organelles. The more than 60 different lysosomal storage diseases are rare diseases; however, collectively, the incidence of lysosomal storage diseases ranges just over 1 in 2500 live births. The majority of lysosomal storage diseases are associated with neurologic manifestations including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. These inborn organelle disorders show wide clinical variability affecting individuals from all age groups. In addition, several of neurologic, also known as neuronopathic, lysosomal storage diseases are associated with some level of white matter disease, which often triggers the diagnostic investigation. Most lysosomal storage diseases are autosomal recessively inherited and few are X-linked, with females being at risk of presenting with mild, but clinically relevant neurologic manifestations. Biochemical assays are the basis of the diagnosis and are usually confirmed by molecular genetic testing. Novel therapies have emerged. However, most affected patients with lysosomal storage diseases have only supportive management to rely on. A better understanding of the mechanisms resulting in the leukodystrophy will certainly result in innovative and efficacious disease-modifying therapies.

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