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La Revue de Medecine Interne Mar 2020Mucopolysaccharidosis are lysosomal storage diseases, secondary to the accumulation of mucopolysaccharides. Type 1 mucopolysaccharidosis is the most common form and... (Review)
Review
Mucopolysaccharidosis are lysosomal storage diseases, secondary to the accumulation of mucopolysaccharides. Type 1 mucopolysaccharidosis is the most common form and affects between 0.69 and 1.66 newborns per 100,000. The severity of mucopolysaccharidosis is variable with lethal forms in utero and attenuated forms diagnosed in adults. The most common symptoms are short stature, facial dysmorphism, chronic articular pains that can mimic chronic inflammatory rheumatism, axial and peripheral bone involvement, hepatosplenomegaly and an early carpal tunnel. Depending on the type of mucopolysaccharidosis, corneal, cerebral or cardiac involvements are possible. Screening is based on the analysis of urinary glycosaminoglycans. The deficient enzyme assay and the gene analysis confirm the diagnosis. Mucopolysaccharidosis recognition is important for patient management and family screening. In addition, specific enzyme replacement therapy exists for certain types of mucopolysaccharidosis. Role of clinician is important to evoke and diagnose mucopolysaccharidosis.
Topics: Adult; Arthritis, Rheumatoid; Diagnosis, Differential; Enzyme Replacement Therapy; Female; Genetic Testing; Humans; Infant, Newborn; Mucopolysaccharidoses; Pregnancy; Prenatal Care; Prognosis
PubMed: 31959364
DOI: 10.1016/j.revmed.2019.11.010 -
Pediatric Endocrinology, Diabetes, and... 2021Mucopolysaccharidoses (MPSs) are known as rare genetic diseases which are caused by mutation in the enzyme heparin sulfate, which normally leads to degradation and... (Review)
Review
Mucopolysaccharidoses (MPSs) are known as rare genetic diseases which are caused by mutation in the enzyme heparin sulfate, which normally leads to degradation and accumulation of glycosaminoglycans in the cells. There are 11 types of MPSs, whereby neuropathy may occur in seven of them (MPS I, II, IIIA, IIIB, IIIC, IIID and VII). Accumulation of degraded heparin sulfate in lysosomes causes cellular dysfunction and malfunction of several organs. However, the exact molecular mechanism how protein degradation and storage leads to cellular dysfunction is not understood, yet. Nonetheless, several genetic and biochemical methods for diagnosis of MPSs are available nowadays. Here we provide an overview on known molecular basis of MPS in general, including enzyme defects and symptoms of MPS; however, the main focus is on MPS type III together with potential and perspective therapy-options.
Topics: Glycosaminoglycans; Humans; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Mutation
PubMed: 34743503
DOI: 10.5114/pedm.2021.109270 -
Indian Journal of Ophthalmology Jul 2022Mucopolysaccharidosis (MPS) is a group of genetic disorders with seven types and 13 subgroups which are characterized by an inherent deficiency of the enzymes... (Review)
Review
Mucopolysaccharidosis (MPS) is a group of genetic disorders with seven types and 13 subgroups which are characterized by an inherent deficiency of the enzymes responsible for the degradation of glycosaminoglycans (GAGs). Defective breakdown of GAG products leads to their widespread accumulation within the lysosomes of various organs involving the eye, central nervous system, skeletal, ocular, nervous, respiratory, cardiac, and the gastrointestinal systems. Clinical spectrum varies from mild systemic and ocular abnormalities with a normal life span to severe phenotype, fatal in the first few months of life. Visual disability due to corneal clouding, retinopathy, and optic nerve involvement causes additional impairment of physical and cognitive functions. Treatment modalities such as bone marrow transplantation and enzyme replacement therapies help in increasing the life span as well as the quality of life of the affected patients. For patients with significant corneal clouding, keratoplasty is the answer. The decision to proceed with keratoplasty is governed by various factors such as the motivation of the patient and his family, other systemic affections and anesthesia concerns. A detailed preoperative counseling should be done regarding the expected visual outcomes in the presence of other ocular comorbidities and the postoperative complication such as graft re-opacification, rejection and glaucoma. Future treatment options such as targeted gene therapy and substrate reduction therapy hold promise to reverse corneal clouding, thereby obviating the need for corneal transplantation. These treatment therapies are still in the experimental stages and human trials are needed to validate their outcomes.
Topics: Corneal Diseases; Corneal Opacity; Corneal Transplantation; Humans; Mucopolysaccharidoses; Quality of Life
PubMed: 35791104
DOI: 10.4103/ijo.IJO_425_22 -
International Journal of Molecular... Feb 2020Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the... (Review)
Review
Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA.
Topics: Bone and Bones; Cartilage; Chondroitin Sulfates; Disease Management; Early Diagnosis; Enzyme Replacement Therapy; Genetic Therapy; Glycosaminoglycans; Hematopoietic Stem Cell Transplantation; Humans; Keratan Sulfate; Lysosomes; Mucopolysaccharidosis III; Mucopolysaccharidosis IV; Nanomedicine; Osteochondrodysplasias; Quality of Life
PubMed: 32102177
DOI: 10.3390/ijms21041517 -
Orphanet Journal of Rare Diseases Oct 2022Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical... (Review)
Review
Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care. However, there are no published standard global clinical care guidelines for patients with Sanfilippo syndrome. To address this, a literature review was conducted to evaluate the current evidence base and to identify evidence gaps. The findings were reviewed by an international steering committee composed of clinical experts with extensive experience in managing patients with Sanfilippo syndrome. The goal was to create a consensus set of basic clinical guidelines that will be accessible to and informed by clinicians globally, as well as providing a practical resource for families to share with their local care team who may not have experience with this rare disease. This review distills 178 guideline statements into an easily digestible document that provides evidence-based, expert-led recommendations for how to approach common management challenges and appropriate monitoring schedules in the care of patients with Sanfilippo syndrome.
Topics: Humans; Child; Mucopolysaccharidosis III; Consensus
PubMed: 36303195
DOI: 10.1186/s13023-022-02484-6 -
International Journal of Molecular... Feb 2020Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter... (Review)
Review
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate. This contributes to a heavy clinical phenotype involving most organ-systems, including the brain, in at least two-thirds of cases. In this review, we will summarize the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. We will also highlight the main open issues related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment.
Topics: Brain; Genes, X-Linked; Humans; Iduronate Sulfatase; Male; Mucopolysaccharidosis II; Phenotype
PubMed: 32070051
DOI: 10.3390/ijms21041258 -
Orphanet Journal of Rare Diseases Jul 2021Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low... (Review)
Review
Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low prevalence and high childhood mortality, researches on mucopolysaccharidoses were mainly focused on the fatal manifestations. With the development of treatments, more and more mucopolysaccharidoses patients were treated by approved therapies, thereby getting prolonged life span and improved quality of life. Abnormal accumulation of glycosaminoglycans in the eye may block trabecular meshwork, thicken sclera and change mechanical behavior of lamina cribrosa, which, by increasing intraocular pressure and damaging optic nerve, could cause glaucoma. Glaucoma was the leading cause of irreversible blindness worldwide, but it was rarely reported in mucopolysaccharidoses patients. Although non-fatal, it seriously affected quality of life. Prevalence of glaucoma in mucopolysaccharidoses patients (ranged from 2.1 to 12.5%) indicated that glaucoma in patients with mucopolysaccharidoses was worthy of attention and further study, thereby improving the quality of life for MPSs patients.
Topics: Child; Glaucoma; Humans; Longevity; Mucopolysaccharidoses; Prevalence; Quality of Life
PubMed: 34266471
DOI: 10.1186/s13023-021-01935-w -
Journal of Applied Genetics Sep 2022Mucopolysaccharidosis (MPS) is a group of 13 hereditary metabolic diseases identified in humans (or 14 diseases if considering one MPS type described to date only in... (Review)
Review
Mucopolysaccharidosis (MPS) is a group of 13 hereditary metabolic diseases identified in humans (or 14 diseases if considering one MPS type described to date only in mice) in which an enzymatic defect results in the accumulation of glycosaminoglycans (GAG) in the lysosomes of cells. First of all, as a result of GAG storage, the proper functioning of the lysosome is disturbed; then, the cells, and finally, tissue, organs, and the whole organism malfunctions are observed. Due to the rarity, heterogeneity, and multi-systemic and progressive nature of MPS, they present a major diagnostic challenge. Due to the wide variation in symptoms and their similarity to other diseases, MPS is often misdiagnosed, usually as neurological diseases (like autism spectrum disorders, psychomotor hyperactivity, and intellectual disability) or rheumatology and orthopedic disorders (like juvenile idiopathic arthritis, Perthes disease, rickets, and muscular dystrophy). In this review article, we present the problems associated with the possibility of misdiagnosing MPS, discuss what diseases they can be confused with, and suggest ways to reduce these problems in the future.
Topics: Animals; Diagnostic Errors; Glycosaminoglycans; Humans; Mice; Mucopolysaccharidoses
PubMed: 35562626
DOI: 10.1007/s13353-022-00703-1 -
JAMA Dermatology Dec 2022
Topics: Humans; Mucopolysaccharidosis II
PubMed: 36260294
DOI: 10.1001/jamadermatol.2022.4049 -
Journal of Inherited Metabolic Disease Jan 2024Current specific treatments for mucopolysaccharidoses (MPSs) include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). Both treatments... (Review)
Review
Current specific treatments for mucopolysaccharidoses (MPSs) include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). Both treatments are hampered by several limitations, including lack of efficacy on brain and skeletal manifestations, need for lifelong injections, and high costs. Therefore, more effective treatments are needed. Gene therapy in MPSs is aimed at obtaining high levels of the therapeutic enzyme in multiple tissues either by engrafted gene-modified hematopoietic stem progenitor cells (ex vivo) or by direct infusion of a viral vector expressing the therapeutic gene (in vivo). This review focuses on the most recent clinical progress in gene therapies for MPSs. The various gene therapy approaches with their strengths and limitations are discussed.
Topics: Humans; Mucopolysaccharidoses; Brain; Genetic Therapy; Enzyme Replacement Therapy; Hematopoietic Stem Cell Transplantation
PubMed: 37204267
DOI: 10.1002/jimd.12626