scholarly journals Mucopolysaccharidosis I type: new management

2019 ◽  
Vol 17 (4) ◽  
pp. 35-42
Author(s):  
S. V. Mikhaylova ◽  
A. N. Slateckay ◽  
E. A. Pristanskova ◽  
K. I. Kirgizov ◽  
O. V. Mendelevich ◽  
...  
Keyword(s):  
Residual Disease ◽  
Upper Airway ◽  
Severe Form ◽  
High Rate ◽  
Skeletal Deformity ◽  
Hematopoietic Stem ◽  
Mucopolysaccharidosis I ◽  
Enzyme Replacement ◽  
Idua Gene ◽  
Mps I

Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2–2.5 years of age, having a high rate of success. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. This review will focus on all these critical issues related to the management of MPS I-H.

scholarly journals Enzyme Replacement Therapy and Hematopoietic Stem Cell Transplantation Results in Patients with Hurler Syndrome: Clinical Cases

2019 ◽  
Vol 18 (3) ◽  
pp. 196-202
Author(s):  
Nato D. Vashakmadze ◽  
Leyla S. Namazova-Baranova ◽  
Natalia V. Zhurkova ◽  
Ekaterina Yu. Zakharova ◽  
Svetlana V. Mikhaylova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Cell Transplantation ◽  
Hurler Syndrome ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is the hereditary disease characterized with alpha-L-iduronidase activity decrease and further accumulation of heparan and dermatan sulfate in lysosomes. MPS I is rare autosomal recessive disorder with incidence of 0.5–4 cases on 100.000 live-birth infants. Meantime there two approaches in MPS I treatment: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). HSCT can be the best option for treatment of patients with severe MPS I (Hurler syndrome). Successful engraftment moderates such clinical signs as obstructive airway diseases, hepatosplenomegaly, cardiovascular system dysfunctions. HSCT prevents cognitive functions decline and other pathologic features of central nervous system. Presented clinical cases show various clinical courses according to age of diagnosis, ERT onset and HSCT implementation.

scholarly journals Lysosomal storage diseases: mucopolysaccharidosis type I and II

2021 ◽  
Vol 12 (3) ◽  
pp. 69-83
Author(s):  
Victoria N. Gorbunova ◽  
Natalia V. Buchinskaia
Keyword(s):  
Severe Form ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Hurler Syndrome ◽  
Mucopolysaccharidosis Type I ◽  
Biochemical Basis ◽  
Hematopoietic Stem ◽  
Genetic Characteristics ◽  
Advantages And Disadvantages ◽  
Mps I

Mucopolysaccharidosis (MPS) are a genetically heterogeneous group of rare monogenic metabolic diseases associated with hereditary insufficiency of lysosomal enzymes involved in the catabolism of glycosaminoglycans, or mucopolysaccharides. The pathogenesis of MPS is due to the accumulation of non-cleaved glycosaminoglycans in lysosomes, which can destroy cells. All MPS are characterized by a polysystemic manifestation, the simultaneous involvement of many organs and tissues in the pathological process, first of all, connective tissues, bones and cartilaginous. This review presents the epidemiology, clinical, biochemical, and molecular genetic characteristics of MPS types I and II, caused by the recessive mutations in the alpha-L-iduronidase and iduronate-2-sulfatase genes, respectively, and by the accumulation of dermatan and heparan sulfate. Each of these diseases is characterized by clinical polymorphism, especially observed in MPS I, which often manifests in a severe form of Hurler syndrome, but can also occur in a milder form of Scheie syndrome. Currently, there is an increased interest in MPS in the world due to the identification of the spectrum and frequencies of mutations in theIDUAandIDSgenes in various populations, including in Russia, and the practical availability of methods for individual molecular diagnostics. The description of the existing experimental models, their role in the study of the biochemical basis of the pathogenesis of these severe hereditary diseases and the development of various therapeutic approaches are given. Discusses the possibility of early diagnosis of MPS I and II types based on neonatal screening in order to increase the effectiveness of their prevention and treatment, as well as the advantages and disadvantages of the main approaches to the treatment of these serious diseases, such as hematopoietic stem cell transplantation, enzyme replacement and substrate-reducing therapy. A clinical example of a combination therapy for a severe form of mucopolysaccharidosis type I Hurler syndrome is presented

scholarly journals Macular Changes in a Mucopolysaccharidosis Type I Patient with Earlier Systemic Therapies

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Augusto Magalhães ◽  
Ana Maria Cunha ◽  
Rodrigo Vilares-Morgado ◽  
Elisa Leão-Teles ◽  
Esmeralda Rodrigues ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Genetic Diagnosis ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I ◽  
Sd Oct ◽  
Systemic Therapies

Purpose. To describe retinal findings in a patient with mucopolysaccharidosis type I (MPS I) that underwent an early treatment with hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). Case Report. We describe a case of a 12-year-old female with a biochemical and genetic diagnosis of MPS I. She underwent HSCT and ERT on the first year of life. The visual acuity was 5/10 in both eyes and she had bilateral grade 2 corneal haze. Spectral domain optical coherence tomography (SD-OCT) revealed thickening of the external limiting membrane (ELM) at the fovea. In the parafoveal and perifoveal regions, SD-OCT displayed a loss of the interdigitation, ellipsoid, and myoid zones and of the ELM accompanied by progressive thinning of the outer nuclear layer. Fundus infrared imaging revealed a hyperreflective ring centred on the fovea and hyporeflective areas in temporal parafoveal regions in both eyes. En face OCT imaging revealed two hyperreflective rings on the outer retinal level. Conclusion. This patient developed macular changes with foveal deposition of hyperreflective material and parafoveal thinning, despite early systemic treatment. Systemic therapies can provide an increase in life expectancy and stabilize visual acuity and corneal clouding, although their effect on retinal degeneration is unknown.

Clinical and economic justification of screening for mucopolysaccharidosis type I in children at groups of risks

2021 ◽  
pp. 4-15
Author(s):  
I. S. Krysanov ◽  
V. S. Krysanova ◽  
V. Yu. Ermakova
Keyword(s):  
Average Cost ◽  
Weighted Average ◽  
Economic Assessment ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Selective Screening ◽  
Mucopolysaccharidosis Type I ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I

Background. Mucopolysaccharidosis Type I (MPS I) has clinical heterogeneity without specific symptoms leading to difficulties with diagnostic on time. In-depth screening for MPS I in children has aim of early detection and timely treatment with an enzyme replacement therapy. Aim. The purpose of this study was to conduct a clinical and economic assessment of the feasibility of screening for MPS I in children at group of risks. Materials and methods. Model for evaluation of the social-economic burden of MPS I with calculation of expenditures has been created. Costs of diagnosed and non-diagnosed patients in group of risks were identified, including direct medical costs (pharmacotherapy, out-patient cure, hospital admission, complications treatment, hematopoietic stem cell transplantation; direct non-medical (payments for disability); indirect (expenses related to the reduction or loss of the ability to work of one of the parents performing the duties of caring for a disabled child). Results. The weighted average cost per 1 diagnosed patient with mild forms of MPS I with selective screening, was 405,974.22 rubles, which is 184,421.85 rubles less vs average cost per 1 undiagnosed patient. The management and treatment of patients with mild forms of MPS I after selective screening will allow saving up to 17.7 million rubles/year, which would possible to additionally screen 705 patients. Taking into account the size of the population of patients with undiagnosed MPS I, currently the costs for this group amount to 56.7 million rubles, while the «overspend» of budget funds for untimely diagnosis of MPS I for this cohort of children is about 22.6 million rubles/year. Conclusion. Selective screening for MPS I in children at group of risks is economically proved and can lead to treatment on-time for disability and complications prevention.

scholarly journals Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5130-5139 ◽  
Author(s):  
Ilaria Visigalli ◽  
Stefania Delai ◽  
Letterio S. Politi ◽  
Carmela Di Domenico ◽  
Federica Cerri ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Manifestations ◽  
Cardiac Insufficiency ◽  
Type I ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps I ◽  
Hsc Transplantation

AbstractType I mucopolysaccharidosis (MPS I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase, which results in glycosaminoglycan accumulation in tissues. Clinical manifestations include skeletal dysplasia, joint stiffness, visual and auditory defects, cardiac insufficiency, hepatosplenomegaly, and mental retardation (the last being present exclusively in the severe Hurler variant). The available treatments, enzyme-replacement therapy and hematopoietic stem cell (HSC) transplantation, can ameliorate most disease manifestations, but their outcome on skeletal and brain disease could be further improved. We demonstrate here that HSC gene therapy, based on lentiviral vectors, completely corrects disease manifestations in the mouse model. Of note, the therapeutic benefit provided by gene therapy on critical MPS I manifestations, such as neurologic and skeletal disease, greatly exceeds that exerted by HSC transplantation, the standard of care treatment for Hurler patients. Interestingly, therapeutic efficacy of HSC gene therapy is strictly dependent on the achievement of supranormal enzyme activity in the hematopoietic system of transplanted mice, which allows enzyme delivery to the brain and skeleton for disease correction. Overall, our data provide evidence of an efficacious treatment for MPS I Hurler patients, warranting future development toward clinical testing.

scholarly journals Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 397
Author(s):  
Lena Provoost ◽  
Carlo Siracusa ◽  
Darko Stefanovski ◽  
Yan Che ◽  
Mingyao Li ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cognitive Abilities ◽  
Treated Group ◽  
Normal Group ◽  
Cognitive Testing ◽  
Mixed Effect ◽  
Mucopolysaccharidosis I ◽  
Clinically Normal ◽  
Idua Gene ◽  
Mps I

Mucopolysaccharidosis I (MPS I) results from a deficiency of a lysosomal enzyme, alpha-L-iduronidase (IDUA). IDUA deficiency leads to glycosaminoglycan (GAG) accumulation resulting in cellular degeneration and multi-organ dysfunction. The primary aims of this pilot study were to determine the feasibility of cognitive testing MPS I affected dogs and to determine their non-social cognitive abilities with and without gene therapy. Fourteen dogs were tested: 5 MPS I untreated, 5 MPS I treated, and 4 clinically normal. The treated group received intrathecal gene therapy as neonates to replace the IDUA gene. Cognitive tests included delayed non-match to position (DNMP), two-object visual discrimination (VD), reversal learning (RL), attention oddity (AO), and two-scent discrimination (SD). Responses were recorded as correct, incorrect, or no response, and analyzed using mixed effect logistic regression analysis. Significant differences were not observed among the three groups for DNMP, VD, RL, or AO. The MPS I untreated dogs were excluded from AO testing due to failing to pass acquisition of the task, potentially representing a learning or executive function deficit. The MPS I affected group (treated and untreated) was significantly more likely to discriminate between scents than the normal group, which may be due to an age effect. The normal group was comprised of the oldest dogs, and a mixed effect logistic model indicated that older dogs were more likely to respond incorrectly on scent discrimination. Overall, this study found that cognition testing of MPS I affected dogs to be feasible. This work provides a framework to refine future cognition studies of dogs affected with diseases, including MPS I, in order to assess therapies in a more comprehensive manner.

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