scholarly journals Molecular Analysis of Vietnamese Patients with Mucopolysaccharidosis Type I

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1162
Author(s):  
Ngoc Thi Bich Can ◽  
Dien Minh Tran ◽  
Thao Phuong Bui ◽  
Khanh Ngoc Nguyen ◽  
Hoang Huy Nguyen ◽  
...  
Keyword(s):  
Autosomal Recessive Disorder ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Direct Dna Sequencing ◽  
Pathogenic Variants ◽  
Vietnamese Population ◽  
Idua Gene ◽  
Classical Characteristic ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by deleterious mutations in the α‑L‑iduronidase (IDUA) gene. Until now, MPS I in Vietnamese has been poorly addressed. Five MPS I patients were studied with direct DNA sequencing using Illumina technology confirming pathogenic variants in the IDUA gene. Clinical characteristics, additional laboratory results, and family history were collected. All patients have presented with the classical characteristic of MPS I, and α‑L‑iduronidase activity was low with the accumulation of glycosaminoglycans. Three variants in the IDUA gene (c.1190‑10C>A (Intronic), c.1046A>G (p.Asp349Gly), c.1862G>C (p.Arg621Pro) were identified. The c.1190‑10C>A variant represents six of the ten disease alleles, indicating a founder effect for MPS I in the Vietnamese population. Using biochemical and genetic analyses, the precise incidence of MPS I in this population should accelerate early diagnosis, newborn screening, prognosis, and optimal treatment

Gene Therapy of Mucopolysaccharidosis Type I Mice: Repeated Administrations and Safety Assessment of pIDUA/Nanoemulsion Complexes

2021 ◽  
Vol 21 ◽  
Author(s):  
Michelle Fraga ◽  
Roselena Silvestri Schuh ◽  
Édina Poletto ◽  
Talita Giacomet de Carvalho ◽  
Raqueli Teresinha França ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Transfection Efficiency ◽  
Signs And Symptoms ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Medium Chain Triglycerides ◽  
Repeated Administrations ◽  
Idua Gene ◽  
Mps I

Background: Mucopolysaccharidosis type I (MPS I) is an inherited disorder caused by α-L-iduronidase (IDUA) deficiency. The available treatments are not effective in improving all signs and symptoms of the disease. Objective: : In the present study, we evaluated the transfection efficiency of repeated intravenous administrations of cationic nanoemulsions associated with the plasmid pIDUA (containing IDUA gene). Methods: Cationic nanoemulsions were composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000) (DSPE-PEG), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), medium chain triglycerides, glycerol, and water and were prepared by high-pressure homogenization and were repeatedly administered to MPS I mice for IDUA production and gene expression. Results: A significant increase in IDUA expression was observed in all organs analyzed, and IDUA activity tended to increase with repeated administrations when compared to our previous report, when mice received a single administration of the same dose. In addition, GAGs were partially cleared from organs, as assessed through biochemical and histology analyzes. There was no presence of inflammatory infiltrate, necrosis, or signs of increase in apoptosis. Furthermore, immunohistochemistry for CD68 showed reduced presence of macrophage cells in treated than in untreated MPS I mice. Conclusion: These set of results suggest that repeated administrations can improve transfection efficiency of cationic complexes without significant increase in toxicity in the MPS I murine model.

scholarly journals Sexual behaviour in a murine model of mucopolysaccharidosis type I (MPS I)

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0220429 ◽  
Author(s):  
Ana Barbosa Mendes ◽  
Cinthia Castro do Nascimento ◽  
Vânia D’Almeida
Keyword(s):  
Sexual Behaviour ◽  
Murine Model ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Mps I

scholarly journals Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

2020 ◽  
Vol 28 (3) ◽  
pp. 279-286
Author(s):  
Camelia Alkhzouz ◽  
Cecilia Lazea ◽  
Diana Miclea ◽  
Carmen Asavoaie ◽  
Ioana Nascu ◽  
...  
Keyword(s):  
Severe Form ◽  
The Other ◽  
Compound Heterozygous ◽  
Type I ◽  
Ophthalmological Examination ◽  
Mucopolysaccharidosis Type ◽  
Hurler Syndrome ◽  
Mucopolysaccharidosis Type I ◽  
Genetic Characteristics ◽  
Mps I

AbstractBackground: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a deficiency of α-L-iduronidase (IDUA), which leads to the accumulation of partially digested glycosaminoglycans (dermatan sulfate and heparan sulfate) in the lysosomes and induces multisystemic alteration. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I. To date, more than 290 IDUA mutations have been reported. The purpose of this study was to present the clinical and genetic characteristics of Romanian MPS I syndrome patients and their genotype-phenotype correlation.Patients and methods: Seven patients (5 girls and 2 boys) with MPS type I, belonging to 4 unrelated families, aged 0,75-17.9 years, were enrolled. The study methods consisted in: clinical and standard auxological assessment, bone radiographs, joint ultrasonography, goniometry, neurological and psychological evaluation, hepatic and splenic ultrasonography, cardiological evaluation, otorhinolaryngology examination, ophthalmological examination, spirometry, α-L-iduronidase enzyme activity assay and molecular analysis.Results: The seven patients originated from 4 unrelated families, three patients with severe, two patients with intermediate and two with attenuated clinical phenotype. Each patient presented the classical picture of MPS type I picture, represented by: variable coarse facial features, arthropathy, hepatosplenomegaly, cardiac involvement, respiratory dysfunction and neurological impairment. Five patological variants, three point mutations (p.Q70 *, p.I238Q and p.K324R), two deletion c.1045_1047delGAC, c.46_57delTCGCTCCTG) and an insertion (c.1389 insC) were identified in both alleles of the ADUA gene in homozygous or heterozygous form. Two novel mutations (p.K324R and c.1389 insC) were reported. The p.Q70*(c.208C>T) variant was identified in 2 families with severe form of disease (Hurler syndrome) in homozygous status in one family and in compound heterozygous status in the other family.Conclusion: The p.Q70* missense variant was the most frequent, correlated in all the cases who presented it with severe form, Hurler syndrome, the other mutations being usually isolated and particular for each patient, associated in our patients with less severe MPS I phenotype, as Hurler-Scheie or Scheie syndrome. The results of this study indicated the mutational heterogeneity of the IDUA gene and the difficulty to indicate some correlation between the genotype and phenotype in MPS I patients.

scholarly journals Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I

2020 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Dawn S. Peck ◽  
Jean M. Lacey ◽  
Amy L. White ◽  
Gisele Pino ◽  
April L. Studinski ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Positive ◽  
Dermatan Sulfate ◽  
False Positive Rate ◽  
False Negative ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Second Tier ◽  
Mps I

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.

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 Mucopolysaccharidosis type I: clinical and biochemical study

2000 ◽  
Vol 6 (2-3) ◽  
pp. 359-366
Author(s):  
H. T. Bassyouni
Keyword(s):  
Enzyme Activity ◽  
Human Genetics ◽  
Biochemical Study ◽  
Clinical Manifestations ◽  
Spot Test ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Inborn Errors ◽  
Mps I

Of 1240 outpatients referred to the Human Genetics Clinic between 1997 and 1998, 248 [20%]had inborn errors of metabolism, 36 [14%] of which were diagnosed as mucopolysaccharidoses. Parental consanguinity was present in 82% of these patients. Deficiency of alpha-L-iduronidase [IDUA] enzyme in leukocytes and increased urinary mucopolysaccharides excretion were detected in 17 patients. The urinary spot test for glucosaminoglycans was inconclusive in 4 of the 17 cases. Results showed a correlation between the biochemical enzyme activity in leukocytes, the amount of excreted mucopolysaccharides and the subtype and course of mucopolysaccharidosis type I. We conclude that estimation of IDUA enzyme activity in leukocytes can differentiate between clinically overlapping cases of MPS I and MPS II and given the clinical manifestations of MPS I is a definitive and unequivocal method of diagnosis while the urinary spot test is inconclusive

scholarly journals Alpha-L-iduronidase deficiency: A novel mutation resulting in severe early presentation of Mucopolyscaridosis type I and litature review of molecular basis

2021 ◽  
Author(s):  
nuha alzaabi ◽  
muneera sirajum ◽  
Mohd Zaki Al-Wawi ◽  
Mohammed Alsuwaiji
Keyword(s):  
Molecular Basis ◽  
Novel Mutation ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Early Presentation ◽  
Idua Gene

The IDUA gene (MIM 252800) provides instructions for producing alpha-L-iduronidase, which is essential for the breakdown of glycosaminoglycans (GAGs). Mutations in the IDUA gene have been found to cause mucopolysaccharidosis type I (MIM 607014). This leads to the accumulation of GAGs within lysosomes causing different organs to be dysfunctional.

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