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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 -
Revista Chilena de Pediatria 2016The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs)... (Review)
Review
The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at lysosomal level. When there is a deficiency of a particular enzyme there is an accumulation of GAGs in the cells resulting in progressive cellular damage, which can affect multiple organ systems and lead to organ failure. Diagnosis is based on knowledge of the clinical manifestations, performing biochemical analyses to identify the type of GAG that is accumulating, and confirm the type of disorder with the corresponding enzymatic determination. Their identification is essential to initiate early treatment, taking into account that multidisciplinary management and enzyme replacement therapy is available for MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), and MPS VI (Maroteaux-Lamy syndrome. In this review, an analysis is made of each of these syndromes, as well as their diagnosis and treatment.
Topics: Animals; Enzyme Replacement Therapy; Glycosaminoglycans; Humans; Mucopolysaccharidoses
PubMed: 26613630
DOI: 10.1016/j.rchipe.2015.10.004 -
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 Orthopaedics Jan 2019Mucopolysaccharidosis (MPS) are rare inherited metabolic diseases, causing lysosomal storage of mucopolysaccharides; clinical presentation involves skeletal system and... (Review)
Review
PURPOSE
Mucopolysaccharidosis (MPS) are rare inherited metabolic diseases, causing lysosomal storage of mucopolysaccharides; clinical presentation involves skeletal system and particularly the spine. Anomalies include developing kyphosis at thoracolumbar junction, that can causes nervous symptoms, and dens hypoplasia with associated atlantoaxial subluxation that can cause myelopathy. We present our experience in the treatment of spine pathology in MPS.
METHODS
Medical treatments of MPS seem to have little impact on spine disease: treatment of cervical instability often includes surgical decompression and stabilization, as in patient MPS1 that we present, while thoracic lumbar kyphosis is treated by bracing and, in severe cases, with surgery. Bracing is more effective in kyphosis under 40° Cobb. Our surgical cases with thoracic lumbar kyphosis over 40° Cobb, treatment include the first one ever described by only posterior approach with vertebrectomy in MPS and a case of lateral costo-transverse approach instrumented correction.
RESULTS
Surgical patients had no major complications after surgery and CT scan at follow-up showed complete fusion without loss of correction, even if in a cervical case we used an adult rigid instrumentation in a four year-and-six month-old girl (11 years follow-up) and in thoracic lumbar kyphosis case treated by vertebrectomy due to diminutive anatomy we positioned interbody cage in suboptimal position.
CONCLUSIONS
Bracing is a viable treatment strategy in thoracic lumbar kyphosis and can obtain good clinical results at medium terms follow-up even if kyphosis deformity remains in radiographs. Surgical treatment is effective in severe evolving cases both at cervical and thoracic lumbar level, main difficulties arose from unavailability of dedicated instrumentation in very young patient, as even smallest devices available are often too big.
Topics: Adult; Braces; Decompression, Surgical; Female; Humans; Infant; Kyphosis; Magnetic Resonance Imaging; Male; Mucopolysaccharidoses; Spinal Cord Diseases; Spinal Diseases; Spinal Fusion; Spine; Tomography, X-Ray Computed
PubMed: 30218179
DOI: 10.1007/s00264-018-4143-0 -
Molecular and Cell Biology of Human... 1995
Review
Topics: Animals; Bone Marrow Transplantation; Central Nervous System; Clinical Trials as Topic; Disease Models, Animal; Genetic Therapy; Humans; Mucopolysaccharidoses
PubMed: 9532574
DOI: 10.1007/978-94-011-0547-7_17 -
International Journal of Molecular... Jan 2020Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes-mucopolysaccharidosis-plus...
Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes-mucopolysaccharidosis-plus syndrome (MPSPS). MPSPS, whose pathophysiology is not elucidated, is an autosomal recessive multisystem disorder caused by a specific mutation p.R498W in the gene. VPS33A functions in endocytic and autophagic pathways, but p.R498W mutation did not affect both of these pathways in the patient's skin fibroblast. Nineteen patients with MPSPS have been identified: seventeen patients were found among the Yakut population (Russia) and two patients from Turkey. Clinical features of MPSPS patients are similar to conventional mucopolysaccharidoses (MPS). In addition to typical symptoms for conventional MPS, MPSPS patients developed other features such as congenital heart defects, renal and hematopoietic disorders. Diagnosis generally requires evidence of clinical picture similar to MPS and molecular genetic testing. Disease is very severe, prognosis is unfavorable and most of patients died at age of 10-20 months. Currently there is no specific therapy for this disease and clinical management is limited to supportive and symptomatic treatment.
Topics: Diagnosis, Differential; Female; Geography; Humans; Male; Mucopolysaccharidoses; Pedigree; Russia; Syndrome
PubMed: 31936524
DOI: 10.3390/ijms21020421 -
Journal of Human Genetics Feb 2019Mucopolysaccharidosis (MPS) is a group of inherited conditions involving metabolic dysfunction. Lysosomal enzyme deficiency leads to the accumulation of... (Review)
Review
Mucopolysaccharidosis (MPS) is a group of inherited conditions involving metabolic dysfunction. Lysosomal enzyme deficiency leads to the accumulation of glycosaminoglycan (GAG) resulting in systemic symptoms, and is categorized into seven types caused by deficiency in one of eleven different enzymes. The pathophysiological mechanism of these diseases has been investigated, indicating impaired autophagy in neuronal damage initiation, association of activated microglia and astrocytes with the neuroinflammatory processes, and involvement of tauopathy. A new inherited error of metabolism resulting in a multisystem disorder with features of the MPS was also identified. Additionally, new therapeutic methods are being developed that could improve conventional therapies, such as new recombinant enzymes that can penetrate the blood brain barrier, hematopoietic stem cell transplantation with reduced intensity conditioning, gene therapy using a viral vector system or gene editing, and substrate reduction therapy. In this review, we discuss the recent developments in MPS research and provide a framework for developing strategies.
Topics: Animals; Combined Modality Therapy; Diagnosis, Differential; Enzyme Replacement Therapy; Genetic Association Studies; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Mucopolysaccharidoses; Phenotype; Prevalence; Research
PubMed: 30451936
DOI: 10.1038/s10038-018-0534-8 -
European Journal of Pharmacology Dec 2020Mucopolysaccharidoses (MPS) represent a devastating group of lysosomal storage diseases (LSD) affecting approximately 1 in 25,000 individuals, where degradation of... (Review)
Review
Mucopolysaccharidoses (MPS) represent a devastating group of lysosomal storage diseases (LSD) affecting approximately 1 in 25,000 individuals, where degradation of glycosaminoglycans (GAG) by lysosomal enzymes is impaired due to mutations causing defects in one of GAG-degrading enzymes. The most commonly used therapy for MPS is enzyme replacement therapy, consisting of application of an active form of the missing enzyme. However, supply of the missing enzyme is not enough in case of MPS types whose symptoms are expressed in central nervous system (CNS), as enzyme does not cross the blood-brain barrier. Moreover, even though enzyme replacement therapy for non-neuronopathic MPS IVA type is approved, it has a limited impact on bone abnormalities, that are one of main symptoms in the disease. Therefore, research into alternative therapeutic approaches for these types of MPS is highly desirable. One such alternative strategy is accelerated degradation of GAG by induction of autophagy. Autophagy is a process of lysosomal degradation of macromolecules that become abnormal or unnecessary for cells. One of the latest discoveries is that GAGs can also be such molecules. Potential drug should also cross blood-brain barrier and be safe in long-term therapy. It seems that one of the polyphenols, resveratrol, can meet the requirements. The mechanism of its action in autophagy stimulation is pleiotropic. Therefore, in this review, we will briefly discuss potential of resveratrol treatment for mucopolysaccharidosis through autophagy stimulation based on research in diseases with similar outcome.
Topics: Animals; Antioxidants; Autophagy; Glycosaminoglycans; Humans; Mucopolysaccharidoses; Resveratrol
PubMed: 32877657
DOI: 10.1016/j.ejphar.2020.173534 -
Molecular Genetics and Metabolism Dec 2017The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific lysosomal enzymes involved in the catabolism of glycosaminoglycans (GAGs). The resulting... (Review)
Review
The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific lysosomal enzymes involved in the catabolism of glycosaminoglycans (GAGs). The resulting GAG accumulation in cells and tissues throughout the body leads to progressive multi-organ dysfunction. MPS patients present with several somatic manifestations, including short stature, musculoskeletal abnormalities, and cardiorespiratory dysfunction, and several primary and secondary neurological signs and symptoms. Epileptic seizures are neurological signs of MPS thought to develop due to accumulation of GAGs in the brain, triggering alterations in neuronal connectivity and signaling, and release of inflammatory mediators. The amount of literature on the prevalence, pathophysiology, clinical features, and management of epileptic seizures in patients with MPS is limited. This review discusses current knowledge on this topic, as well as two case examples, presented and discussed during a closed meeting on MPS and the brain among an international group of experts with extensive experience in managing and treating MPS.
Topics: Adolescent; Anticonvulsants; Brain; Child; Electroencephalography; Epilepsy; Female; Glycosaminoglycans; Humans; Magnetic Resonance Imaging; Male; Mucopolysaccharidoses; Prevalence; Treatment Outcome
PubMed: 29170080
DOI: 10.1016/j.ymgme.2017.10.006