scholarly journals Ophthalmological Findings in Mucopolysaccharidoses

2019 ◽  
Vol 8 (9) ◽  
pp. 1467 ◽  
Author(s):  
Shizuka Tomatsu ◽  
Susanne Pitz ◽  
Ulrike Hampel
Keyword(s):  
Focal Point ◽  
Childhood Mortality ◽  
Research Progress ◽  
Type I ◽  
Lysosomal Storage ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Ocular Manifestations ◽  
Corneal Clouding ◽  
Low Incidence

The mucopolysaccharidoses (MPS) are a heterogenous group of lysosomal storage disorders caused by the accumulation of glycosaminoglycans (GAGs). The accrual of these compounds results in phenotypically varied syndromes that produce multi-organ impairment with widespread systemic effects. The low incidence of MPS (approximately 1/25,000 live births) in conjunction with the high childhood mortality rate had limited the availability of research into certain clinical features, especially ocular manifestations. As the recent successes of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have greatly increased life expectancy in these patients, they have served as a focal point for the transition of research towards improvement of quality of life. Ophthalmological findings in MPS include corneal clouding, glaucoma, optic neuropathies, and retinopathies. While corneal clouding is the most common ocular feature of MPS (especially type I, IVA, and VI), its response to HSCT and ERT is minimal. This review discusses known eye issues in the MPS subtypes, diagnosis of these ocular diseases, current clinical and surgical management, noteworthy research progress, and ultimately presents a direction for future studies.

scholarly journals Differences in MPS I and MPS II Disease Manifestations

2021 ◽  
Vol 22 (15) ◽  
pp. 7888
Author(s):  
Christiane S. Hampe ◽  
Brianna D. Yund ◽  
Paul J. Orchard ◽  
Troy C. Lund ◽  
Jacob Wesley ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Treatment Options ◽  
Neurological Involvement ◽  
Type I ◽  
Ionic Balance ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Corneal Clouding ◽  
Mps I

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

2019 ◽  
Vol 103 (3) ◽  
pp. 315-326 ◽  
Author(s):  
Aaron W Winter ◽  
Ali Salimi ◽  
Luis H Ospina ◽  
Jonathan C P Roos
Keyword(s):  
Gaucher Disease ◽  
Substrate Reduction Therapy ◽  
Type I ◽  
Lysosomal Storage ◽  
Ocular Abnormalities ◽  
Enzyme Replacement ◽  
Ocular Manifestations ◽  
Ophthalmic Manifestations ◽  
Increased Risk ◽  
Risk Of Malignancy

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

scholarly journals Management of Corneal Clouding in Patients with Mucopolysaccharidosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3263
Author(s):  
Orlaith McGrath ◽  
Leon Au ◽  
Jane Ashworth
Keyword(s):  
Corneal Transplantation ◽  
Research Progress ◽  
Definitive Treatment ◽  
Lamellar Keratoplasty ◽  
Deep Anterior Lamellar Keratoplasty ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Corneal Clouding ◽  
Organ Systems ◽  
Anterior Lamellar Keratoplasty

Mucopolysaccharidoses (MPS) are a rare group of lysosomal storage disorders characterized by the accumulation of incompletely degraded glycosaminoglycans (GAGs) in multiple organ systems including the eye. Visual loss occurs in MPS predominantly due to corneal clouding and retinopathy, but the sclera, trabecular meshwork and optic nerve may all be affected. Despite the success of therapies such as enzyme replacement therapy (ERT) and hematopoietic stem-cell transplantation (HSCT) in improving many of the systemic manifestations of MPS, their effect on corneal clouding is minimal. The only current definitive treatment for corneal clouding is corneal transplantation, usually in the form of a penetrating keratoplasty or a deep anterior lamellar keratoplasty. This article aims to provide an overview of corneal clouding, its current clinical and surgical management, and significant research progress.

scholarly journals Mucopolysaccharidosis Type I in Children, a Forgotten Diagnosis Responsible for Undiagnosed Musculoskeletal Complaints: Report of Two Cases

2019 ◽  
Vol 62 (4) ◽  
pp. 161-165
Author(s):  
Soheila Hoseinzadeh Moghadam ◽  
Masood Ghahvechi ◽  
Fatemeh Mozafari ◽  
Fatemeh Sayarifard ◽  
Mahdieh-Sadat Mousavi ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Type I ◽  
Musculoskeletal Complaints ◽  
Lysosomal Storage ◽  
Multiple Systems ◽  
Enzyme Replacement ◽  
Presenting Symptoms ◽  
Key Factor ◽  
Delays In Diagnosis ◽  
Clinical Conditions

Mucopolysaccharidoses (MPS) are a subgroup of lysosomal storage disorders. The underlying mechanism of MPS disorders are deficiency in specific enzymes which leads to accumulation of partially degraded glycosaminoglycans (GAGs) in various tissues. A wide variety of manifestations are reported but musculoskeletal complaints are common among them. In milder forms of MPS, musculoskeletal complaints are presenting symptoms. Delays in diagnosis due to unspecific and mild symptoms is common. Misdiagnosis of MPS as juvenile idiopathic arthritis and other inflammatory arthritis disorders is frequent. Early diagnosis and treatment prevents irreversible cellular damages and is a key factor in efficacy of enzyme replacement therapy. In this study we described two MPS patients with musculoskeletal complaints who were not diagnosed for a period of time. Although musculoskeletal manifestation are common in a variety of clinical conditions, their presence at low ages or co-occurrence of other manifestations (such as cardiac, respiratory, neurologic, etc.) in multiple systems should prompt evaluation of patients for MPS and other metabolic disorders. The rheumatologists’ awareness on MPS should be promoted to achieve timely diagnosis and subsequent early treatment.

scholarly journals REDUCED DOSING REGIMEN OF ENZYME REPLACEMENT THERAPY IN ADULT PATIENTS WITH TYPE I GAUCHER DISEASE: PRELIMINARY RESULTS

2019 ◽  
Vol 64 (3) ◽  
pp. 331-341 ◽  
Author(s):  
R. V. Ponomarev ◽  
K. A. Lukina ◽  
E. P. Sysoeva ◽  
R. B. Chavynchak ◽  
A. A. Solovyeva ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Lysosomal Storage Diseases ◽  
Adult Patients ◽  
Type I ◽  
Treatment Goals ◽  
Lysosomal Storage ◽  
Current Standard ◽  
Enzyme Replacement

Introduction. Gaucher disease (GD) belongs to the group of lysosomal storage diseases. Enzyme replacement therapy (ERT) is considered to be the current standard in GD treatment. No reduced ERT regimen has thus far been developed. Aim. To develop an optimal reduced ERT regimen for adult patients with type I GD, which is scientifically and economically viable.Materials and methods. The study included 100 adult patients with type I GD who achieved treatment goals following at least two years of the standard ERT regimen. Patients were prescribed a reduced ERT regimen, which consisted in increasing the interval between the infusions of the recombinant enzyme up to 4 weeks, at a dose of 15–20 units/kg of body weight. The efficacy of the reduced ERT regimen was assessed once every 12 months according to main GD parameters. The follow-up period in the study ranged from 12 to 36 months.Results. The patients with type I GD who achieved treatment goals following the standard ERT regimen and were then prescribed a reduced ERT regimen retained a stable therapeutic effect of the initial treatment according to all parameters: no clinically significant differences found in haemoglobin and platelet levels, spleen size and specific infiltration of femur bone marrow.Conclusion. An increase in the intervals between infusions of the recombinant glucocerebrosidase up to 4 weeks for 12, 24 and 36 months did not lead to worsening of the laboratory and instrumental parameters associated with GD. 

scholarly journals Gaucher Disease Type I: A Case Report

2020 ◽  
Vol 47 (3) ◽  
pp. 22-25
Author(s):  
D. Nikolova ◽  
A. Yordanov ◽  
V. Damyanova ◽  
A. Yavorova ◽  
A. Radinov
Keyword(s):  
Gaucher Disease ◽  
Clinical Symptoms ◽  
Systemic Disease ◽  
Disease Type ◽  
Type I ◽  
Lysosomal Storage ◽  
Laboratory Findings ◽  
Enzyme Replacement ◽  
Targeted Analysis ◽  
Laboratory Test Results

AbstractGaucher disease (GD) is a multi-systemic disease with a low population frequency. It is a lysosomal storage disorder (LSD) that causes accumulation of glucocerebroside in the so called Gaucher cells predominantly in areas like the spleen, liver and bone marrow. Type I GD (GDI) is the most common form and usually does not involve the brain and the spinal cord. The symptoms can range from mild to severe and may appear anytime from childhood to adulthood. Diagnostics can often be challenging and imposes looking at person’s medical history, symptoms, physical exam, and laboratory test results. We present a difficult to diagnose case of a 34-year-old woman admitted to the Clinic of Hematology, “Sv. I. Rilski” hospital with splenomegaly, normal laboratory findings and non-enlarged liver. She didn’t show focal neurological symptoms. A series of tests were assigned including genetic targeted analysis. The case is an example of a rare genetic disease with mild clinical symptoms. Diagnosis of Gaucher disease, type I was confirmed by measurement of a GBA enzyme activity and identification of mutations in the GBA gene inherited in an autosomal recessive manner. Thanks to the efforts of the clinical team, the assignment of adequate clinical and laboratory tests and their correct interpretation, the patient was subjected to enzyme replacement therapy (ERT). Although the diagnosis was settled relatively late (at 34 years of age), the correct therapy slowed down the invalidation and improved the quality of life of the patient.

scholarly journals Surgical Management of Spinal Disorders in People with Mucopolysaccharidoses

2020 ◽  
Vol 21 (3) ◽  
pp. 1171
Author(s):  
Hidetomi Terai ◽  
Hiroaki Nakamura
Keyword(s):  
Surgical Management ◽  
Bone Growth ◽  
Soft Tissues ◽  
Atlantoaxial Instability ◽  
Lysosomal Storage ◽  
Hematopoietic Stem ◽  
Spinal Disorders ◽  
Enzyme Replacement ◽  
Therapeutic Modalities ◽  
Canal Stenosis

Mucopolysaccharidoses (MPS) are a group of inherited, multisystem, lysosomal storage disorders involving specific lysosomal enzyme deficiencies that result in the accumulation of glycosaminoglycans (GAG) secondary to insufficient degradation within cell lysosomes. GAG accumulation affects both primary bone formation and secondary bone growth, resulting in growth impairment. Typical spinal manifestations in MPS are atlantoaxial instability, thoracolumbar kyphosis/scoliosis, and cervical/lumbar spinal canal stenosis. Spinal disorders and their severity depend on the MPS type and may be related to disease activity. Enzyme replacement therapy or hematopoietic stem cell transplantation has advantages regarding soft tissues; however, these therapeutic modalities are not effective for bone or cartilage and MPS-related bone deformity including the spine. Because spinal disorders show the most serious deterioration among patients with MPS, spinal surgeries are required although they are challenging and associated with high anesthesia-related risks. The aim of this review article is to provide the current comprehensive knowledge of representative spinal disease in MPS and its surgical management, including the related pathology, symptoms, and examinations.

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