arsB Genes Research Articles

Arsenic efflux and bioremediation potential of Klebsiella oxytoca via the arsB gene.

Arsenic-resistant Klebsiella oxytoca strain AT-02 was isolated from the ground water of the Multan region of Pakistan. The strain displayed high arsenite and arsenate resistance as minimal inhibitory concentration (MIC) was 600ppm and 10,000ppm respectively. The high tolerance of the isolated strain towards arsenate can be postulated due to significant increase in biofilm in response to arsenate. The bacterial strain exposed to 1/2 and 3/4 MIC showed a significant 10 and 12 folds increase in expression of the arsenite efflux gene arsB. Sequential and structural comparison of the arsB gene showed the presence of conserved arsenic binding residues. Arsenic remediation by AT-02 biomass was 50% after 0.5 hours of incubation and 66% in 2 hours. the increase in remediation efficiency with the increase in incubation time indicates its biosorption potential. the arsenic sensitive strain NK11 showed only 4-5% arsenic remediation. Fourier transform infrared spectroscopy (FTIR) analysis confirmed interaction of arsenate and arsenite with functional groups (aromatic amino acid residues) on the cell surface leading to characteristic peak shifts. Thus, the isolated AT-02 has the potential to remediate both arsenite and arsenate from contaminated environmental sites.

Agricultural Soil as a Reservoir of Pseudomonas aeruginosa with Potential Risk to Public Health.

Pseudomonas aeruginosa is an opportunistic pathogen with a high capacity to adapt to different factors. The aim of this study is to analyze the pathogenicity in P. aeruginosa strains and their resistance to heavy metals and antibiotics, in agricultural soil of the state of Tamaulipas, Mexico. Susceptibility to 16 antibiotics was tested using the Kirby-Bauer method (CLSI). Eight virulence factors (FV) and six genes associated with heavy metal resistance were detected by PCR. As a result, P. aeruginosa was detected in 55% of the samples. The eight virulence factors were identified in ≥80% of the strains. The strains showed some level of resistance to only three antibiotics: 32.8% to ticarcillin, 40.8% to ticarcillin/clavulanic acid and 2.4% to aztreonam. The most frequent heavy metal resistance genes were arsC (92.8%) and copA (90.4%). However, copB and arsB genes were also identified in a percentage greater than 80%, and the least frequent genes were merA in 14.4% and czcA in 7.2%. Although P. aeruginosa strains showed a high percentage of factor virulence (potential ability to cause infections), their high levels of susceptibility to antibiotics lead to the assumption that infections are easily curable.

The importance of geographic and sociodemographic aspects in the characterization of mucopolysaccharidoses: a case series from Ceará state (Northeast Brazil).

Geographic and sociodemographic aspects may influence the natural history and epidemiology of mucopolysaccharidoses (MPS). The main objective in this work was to evaluate the clinical, molecular, and geographic profile of MPS in a population from Ceará (Northeast Brazil). For this, we have performed a descriptive cross-sectional study based on clinical evaluation, interviews with patients and/or family members, and review of medical records of 76 MPS patients. MPS II was the most common type, with the most affected individuals presenting missense pathogenic variants. Patients with MPS I proved to be the most severe clinical phenotype, presenting the first symptoms (mean: 7.1 months; SD = 4.5) and being diagnosed earlier (2.2 years; SD = 2.1) in comparison with the other types. In addition, we have shown that 13 individuals with MPS VI were born of consanguineous marriages in small, nearby cities, in a place where geographical isolation, consanguinity, and clusters of genetic diseases were previously reported. Ten of these individuals (at least, seven different families) presented a rare pathogenic variant in the ARSB gene, c.1143-8T > G in homozygosity, previously reported only among Iberian and South American patients. The results presented here provide a comprehensive picture of MPS in an important state of the Brazilian Northeast, a region that concentrates many risk factors for rare genetic diseases, such as endogamy, inbreeding, and reproductive isolation. We discuss the possible evolutionary processes and biosocial dynamics that can help to explain this finding in terms of population medical genetics and public health.

Efficient production of 3-fucosyllactose in a plasmid-free engineered Escherichia coli through strengthening of the GDP-fucose pathway

Human milk oligosaccharides (HMOs) are bioactive oligosaccharides with characterization of complexity and indigestion, which support the progress of immune system, gut microenvironment, and brain in infants. In this work, 3-fucosyllactose (3-FL) was successfully synthesized in recombinant plasmid-free Escherichia coli by strengthening GDP-l-fucose pathway. For this, the native promoters of manB, manC, gmd, and wcaG in chromosome of E. coli were replaced by PJ23119, a constitutive promoter. To further increase the 3-FL production, multiple copies of fut3Bc (encoding α1,3-fucosyltransferase from Neobacillus cucumis) were integrated into the genome of engineered strains to replace the native genes arsB, ldhA, poxB, and manXYZ, respectively. The titer of 3-FL was boosted to 3.17 g/L via overexpressing manA with promoter PJ23119 in chromosome of the engineered hosts. Ultimately, in a 5 L bioreactor, the titer of 3-FL achieved 28.13 g/L by fed-batch culture at 60 h, with a productivity of 0.54 g/L/h and a yield of 0.95 mol/mol lactose, without using plasmids and antibiotics. Importantly, only 3-FL could be synthesized in fut3Bc-based strains without producing other HMOs, showing great potential in either the purity or productivity.

Biotransformation of roxarsone by earthworms and subsequent risk of soil arsenic release: The role of gut bacteria

The organoarsenical feed additive roxarsone (ROX) is a ubiquitous threat due to the unpredictable levels of arsenic (As) released by soil bacteria. The earthworms representing soil fauna communities provide hotspots for As biotransformation genes (ABGs). Nonetheless, the role of gut bacteria in this regard is unclear. In this study, the changes in As speciation, bacterial ABGs, and communities were analyzed in a ROX-contaminated soil (50 mg/kg As in ROX form) containing the earthworm Eisenia feotida. (RE vs. R treatment). After 56 d, earthworms reduced the levels of both ROX and total As by 59 % and 17 %, respectively. The available As content was 10 % lower in the RE than in R treatment. Under ROX stress, the total ABG abundance was upregulated in both earthworm gut and soil, with synergistic effects observed following RE treatment. Besides, the enrichment of arsM and arsB genes in earthworm gut suggested that gut bacteria may facilitate As removal by enhancing As methylation and transport function in soil. However, the bacteria carrying ABGs were not associated with the ABG abundance in earthworm gut indicating the unique strategies of earthworm gut bacteria compared with soil bacteria due to different microenvironments. Based on a well-fit structural equation model (P = 0.120), we concluded that gut bacteria indirectly contribute to ROX transformation and As detoxification by modifying soil ABGs. The positive findings of earthworm-induced ROX transformation shed light on the role of As biomonitoring and bioremediation in organoarsenical-contaminated environments.

Genetic predisposition to differentiated thyroid cancer in the Polish population.

Genome sequencing technologies reveal molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing data. We analyzed sequencing data from 1076 unrelated individuals totaling over 1018 billion read pairs and yielding an average 35.26 × read depth per genome, released openly for academic and clinical research as the Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort was compared with the frequency estimated for the non‑Finnish European population obtained from the gnomAD database (gnomad.broadinstitute.org). Significant differences in variant frequency were found for the APC, ARSB, ATM, BRCA1, CHEK2, DICER1, GPD1L, INSR, KCNJ10, MYH9, PALB2, PLCB1, PLEKHG5, PTEN, RET, SEC23B, SERPINA1, SLC26A4, SMAD3, STK11, TERT, TOE1, and WRN genes. Even though the Polish population is genetically similar to the other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as those in the RET, CHEK2, BRCA1, SLC26A4, or TERT genes. Further studies are needed to identify genomic variants associated directly with DTC.

Detection of inversion with breakpoints in ARSB causing MPS VI by whole-genome sequencing: lessons learned and best practices.

Mucopolysaccharidosis type VI (MPSVI), an autosomal recessive lysosomal storage disorder caused by pathogenic variants in ARSB gene. Usually, whole exome sequencing (WES) can identify these variants, and if WES failed to detect causative variants, whole-genome sequencing (WGS) may be considered to investigate deep intronic variations and structural alterations in patients. Whole-exome sequencing (WES) and whole genome sequencing (WGS) were performed in a Chinese family having a boy with suspected diagnosis of MPS with macrocephaly, coarse facial features, broad forehead, thick lips, frontal bossing, craniosynostosis, blue spots, frequent upper respiratory infections, inguinal hernia, and dysostosis multiplex. Lysosomal enzymatic assays for leucocytes were used to assess the activity of arylsulfatase B of the boy's leucocytes. Sanger sequencing and karyotyping analysis were used to validate the variants identified in the boy and his parents. This boy diagnosed with MPSVI based on clinical phenotypes and laboratory biochemical assays, and WES identified only a maternally inherited missense variant, c.908G>T (p.Gly303Val), in the ARSB gene. By performing WGS, we found a paracentric inversion involving chromosome 5q14.1q13.2 (78180730-138771424 inv), disrupting the ARSB gene on the proband and his father. The inversion was confirmed through karyotyping analysis, and the breakpoints were validated by agarose gel electrophoresis and Sanger sequencing. This study reminds us that WGS should be done when WES failed to achieve a molecular diagonosis, and it also underscores the importance of WGS especially in cases of high clinical suspicion.

Generation of induced pluripotent stem cell line (RCMGi012-A) from fibroblasts of patient with mucopolysaccharidosis type VI

Skin fibroblasts obtained from a 5-year-old girl with genetically proven (two heterozygous mutations in ARSB gene) and clinically manifested mucopolysaccharidosis type VI were successfully transformed into induced pluripotent stem cells by using Sendai virus-based reprogramming vectors including the four Yamanaka factors namely SOX2, OCT3/4, KLF4, and c-MYC. These iPSCs expressed pluripotency markers, had a normal karyotype and the potential to differentiate into three germ layers in spontaneous differentiation assay. The line may be used for cell differentiation and pharmacological investigations, and also may provide a model for development of a personalized treatment including drug screening and genome editing.

Genetic and environmental factors driving congenital solitary functioning kidney.

Congenital solitary functioning kidney (CSFK) is an anomaly predisposing to hypertension, albuminuria and chronic kidney disease. Its aetiology is complex and includes genetic and environmental factors. The role of gene-environment interactions (G×E), although relevant for other congenital anomalies, has not yet been investigated. Therefore, we performed a genome-wide G×E analysis with six preselected environmental factors to explore the role of these interactions in the aetiology of CSFK. In the AGORA (Aetiologic research into Genetic and Occupational/environmental Risk factors for Anomalies in children) data- and biobank, genome-wide single-nucleotide variant (SNV) data and questionnaire data on prenatal exposure to environmental risk factors were available for 381 CSFK patients and 598 healthy controls. Using a two-step strategy, we first selected independent significant SNVs associated with one of the six environmental risk factors. These SNVs were subsequently tested in G×E analyses using logistic regression models, with Bonferroni-corrected P-value thresholds based on the number of SNVs selected in step one. In step one, 7-40 SNVs were selected per environmental factor, of which only rs3098698 reached statistical significance (P=.0016, Bonferroni-corrected threshold 0.0045) for interaction in step two. The interaction between maternal overweight and this SNV, which results in lower expression of the Arylsulfatase B (ARSB) gene, could be explained by lower insulin receptor activity in children heterozygous for rs3098698. Eight other G×E interactions had a P-value <.05, of which two were biologically plausible and warrant further study. Interactions between genetic and environmental factors may contribute to the aetiology of CSFK. To better determine their role, large studies combining data on genetic and environmental risk factors are warranted.

Elucidating the functional impact of G137V and G144R variants in Maroteaux Lamy's Syndrome by Molecular Dynamics Simulation.

Mucopolysaccharidoses VI (Maroteaux Lamy syndrome) is a metabolic disorder due to the loss of enzyme activity of N-acetyl galactosamine-4-sulphatase arising from mutations in the ARSB gene. The mutated ARSB is the origin for the accumulation of GAGs within the lysosome leading to severe growth deformities, causing lysosomal storage disease. The main focus of this study is to identify the deleterious variants by applying bioinformatics tools to predict the conservation, pathogenicity, stability, and effect of the ARSB variants. We examined 170 missense variants, of which G137V and G144R were the resultant variants predicted detrimental to the progression of the disease. The native along with G137V and G144R structures were fixed as the receptors and subjected to Molecular docking with the small molecule Odiparcil to analyze the binding efficiency and the varied interactions of the receptors towards the drug. The interaction resulted in similar docking scores of -7.3kcal/mol indicating effective binding and consistent interactions of the drug with residues CYS117, GLN118, THR182, and GLN517 for native, along with G137V and G144R structures. Molecular Dynamics were conducted to validate the stability and flexibility of the native and variant structures on ligand binding. The overall study indicates that the drug has similar therapeutic towards the native and variant based on the higher binding affinity and also the complexes show stability with an average of 0.2nm RMS value. This can aid in the future development therapeutics for the Maroteaux Lamy syndrome.

Leukocyte Imbalances in Mucopolysaccharidoses Patients.

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the IDS gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. In MPS VI, there is dermatan sulfate lysosomal accumulation due to pathogenic mutations in the ARSB gene, leading to arylsulfatase B deficiency. Alterations in the immune system of MPS mouse models have already been described, but data concerning MPSs patients is still scarce. Herein, we study different leukocyte populations in MPS II and VI disease patients. MPS VI, but not MPS II patients, have a decrease percentage of natural killer (NK) cells and monocytes when compared with controls. No alterations were identified in the percentage of T, invariant NKT, and B cells in both groups of MPS disease patients. However, we discovered alterations in the naïve versus memory status of both helper and cytotoxic T cells in MPS VI disease patients compared to control group. Indeed, MPS VI disease patients have a higher frequency of naïve T cells and, consequently, lower memory T cell frequency than control subjects. Altogether, these results reveal MPS VI disease-specific alterations in some leukocyte populations, suggesting that the type of substrate accumulated and/or enzyme deficiency in the lysosome may have a particular effect on the normal cellular composition of the immune system.

The articular and the craniocervical abnormalities are of confusing age of onset in patients with Maroteaux-Lamy disease (MPS VI).

Maroteaux-Lamy disease (MPS Type VI) is an autosomal recessive lysosomal storage disorder. Skeletal abnormalities are vast. Early recognition may facilitate timely diagnosis and intervention, leading to improved patient outcomes. The most challenging is when patients manifest a constellation of craniocervical and articular deformities with variable age of onset. We collected 15 patients with MPS VI (aged from 6 years-58 years). From within our practice in Pediatric Orthopedics, we present patients with MPS type VI who were found to manifest a diverse and confusing clinical presentation of hip deformities and cervical cord compression. Stem cell transplants were proposed as treatment tool and enzyme replacement therapy has been instituted in some patients. The spectrum of the clinical involvement in our group of patients was supported firstly via the clinical phenotype followed by assessment of the biochemical defect, which has been detected through the deficiency of N-acetylgalactosamine-4-sulfatase (arylsulphatase B) leading to increased excretion of dermatan sulphate. Secondly, through the molecular genetic results, which showed homozygous or compound heterozygous mutation in the ARSB gene on chromosome 5q14. Hip replacements and decompression operations have been performed to restore function and to alleviate pain in the former and life saving procedure in the latter. The efforts in searching for the etiological diagnosis in patients with skeletal dysplasia/MPSs has not been rewarding as many had anticipated. This emerged from several facts such as improper clinical documentation, missing diagnostic pointers in radiographic interpretations, limited knowledge in skeletal dysplasia and its variants, and the reliance on underpowered studies. Physicians and radiologists are required to appreciate and assess the diverse phenotypic and the radiographic variability of MPS VI. The importance of considering MPS in the differential diagnosis of other forms skeletal dysplasia is mandatory. Finally, we stress that the value of early diagnosis is to overcome dreadful complications.

Bacterial coculture enhanced Cd sorption and As bioreduction in co-contaminated systems.

The bacterial interactions that regulate Cd sorption and As bioreduction in co-contaminated systems are poorly understood. We isolated two bacterial strains, i.e., Pseudomonas aeruginosa and Bacillus licheniformis from a Cd and As co-contaminated soil and compared the effects of monoculture and coculture on microbial Cd sorption and As bioreduction efficiency in the media with different Cd (0, 0.5, 5, 10, 50, 100mg/L) and As(Ⅴ) (0, 90mg/L) concentrations. Compared with monoculture, the bacterial coculture increased the Cd sorption efficiency by up to 32% and the As bioreduction (As(Ⅴ) to As(Ⅲ)) efficiency by up to 28%, associated with the increased abundance of As reduction gene arsB. Based on SEM-TEM and metabolomics, the enhanced efficiency was attributed to bacterial interactions, supported by the differential secretion of extracellular polymeric substances. Notably, the differential lipids and lipid-like molecules, and organoheterocyclic compounds resulted from bacterial interactions compared to monoculture exhibited the highest Cd sorption and As bioreduction. The increased efficiencies by bacterial coculture were verified by soil incubation experiments. These results provide insight on applying specific bacterial coculture and their metabolites to enhance Cd sorption and As bioreduction in effective and sustainable remediation of co-contaminated environments.

Soil pH determines arsenic-related functional gene and bacterial diversity in natural forests on the Taibai Mountain

Arsenic-related functional genes are ubiquitous in microbes, and their distribution and abundance are influenced by edaphic factors. In arsenic-contaminated soils, soil arsenic content and pH determine the distribution of arsenic metabolizing microorganisms. In the uncontaminated natural ecosystems, however, it remains understudied for the key variable factor in determining the variation of bacterial assembly and mediating the arsenic biogeographical cycles. Here, we selected natural forest soils from southern and northern slopes along the altitudinal gradient of Taibai Mountain, China. The arsenic-related functional genes and soil bacterial community was examined using GeoChip 5.0 and high-throughput sequencing of 16S rRNA genes, respectively. It was found that arsenic-related functional genes were ubiquitous in tested forest soils. The gene arsB has the highest relative abundance, followed by arsC, aoxB, arrA, arsM, and arxA. The arsenic-related functional genes distribution on two slopes were decoupled from their corresponding bacterial community. Though there are higher abundance of bacterial communities on the northern slope than that on the southern slope, for arsenic-related functional genes, the abundance has the contrary trend which showing the more arsenic-related functional genes on the southern slope. In the top ten phyla, Proteobacteria and Actinobacteria were dominant phyla which affected the abundance of arsenic-related functional genes. Redundancy analysis and variance partitioning analysis indicated that soil pH, organic matter and altitude jointly determined the arsenic-related functional genes diversity in the two slopes of Taibai Mountain, and soil pH was a key factor. This indicates that the lower pH may shape more microbes with arsenic metabolic capacity. These findings suggested that soil pH plays a significant role in regulating the distribution of arsenic-related functional microorganisms, even for a forest ecosystem with an altitudinal gradient, and remind us the importance of pH in microbe mediated arsenic transformation.

Genotype by environment interactions for chronic wasting disease in farmed US white-tailed deer.

Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically. Herein, we perform the largest genome-wide association analysis to date for chronic wasting disease (n = 412 chronic wasting disease-positive; n = 758 chronic wasting disease-nondetect) using a custom Affymetrix Axiom single-nucleotide polymorphism array (n = 121,010 single-nucleotide polymorphisms), and confirm that differential susceptibility to chronic wasting disease is a highly heritable () polygenic trait in farmed US white-tailed deer, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P ≤ 3.19E-08; phenotypic variance explained ≥ 0.025) across 3 US regions (Northeast, Midwest, South). However, 20 chronic wasting disease-positive white-tailed deer possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant single-nucleotide polymorphisms (P-value ≤ 5E-05) implicating ≥24 positional candidate genes; many of which have been directly implicated in Parkinson’s, Alzheimer’s and prion diseases. Genotype-by-environment interaction genome-wide association analysis revealed a single-nucleotide polymorphism in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on chronic wasting disease (P ≤ 3.20E-06); with increasing copy number of the minor allele increasing susceptibility to chronic wasting disease in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant genotype-by-environment single-nucleotide polymorphisms (P-value ≤ 5E-05) were also detected, thereby implicating ≥ 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson’s, Alzheimer’s, and prion diseases.

Isolation and Characterization of As (V)-reducing Bacillus sp. Strain SM-B1 from Arsenic Laden Gold Mine in Malaysia

Arsenic is a highly toxic element released into the environment naturally or through human activities. Bacteria are equipped with detoxification mechanisms that enable them to cope with the adverse effects of arsenic. These mechanisms play an important role in biogeochemical cycling of arsenic in the environment. Therefore, this study aimed to isolate arsenic resistant bacteria from arsenic-laden soils in a Malaysian gold mining environment and to characterize their arsenic-transformation ability. Culture enrichment was carried out in LB medium supplemented with As (III) or As (V), resulting in isolation of two bacterial strains. Bacillus sp. SM-B1 showed tolerance to 30 mM As (III) and 350 mM As (V). Acinetobacter sp. SM-S1 demonstrated tolerance to 25 mM As (III) and 300 mM As (V). Bacillus sp. SM-B1 completely reduced 1 mM As (V) in 36 h under aerobic conditions. Putative fragments of arsC and arsB gene were amplified from the genome of isolate SM-B1. Acinetobacter sp. SM-S1 did not show any arsenic transformation activity. Bacillus sp. SM-B1 grown at pH 9 showed potential in arsenic accumulation. Findings generated from this study provide additional details on arsenic-transforming bacteria associated with high arsenic soil and their roles in arsenic biogeochemical cycle in arsenic-contaminated mines in Malaysia.

A novel nonsense MPS VI mutation in a south Moroccan patient

A 12-years-old, Moroccan child with a history of skeletal deformities, gait disorder, Short stature, valvulopathy, facial dysmorphy, corneal opacity, umbilical hernia, and hepatomegaly. He has onset from birth, delayed first milestones (setting, gait, and language) and severe dysostosis multiplex. Elevated urinary glycosaminoglycans concentration was found, enzymatic assays show a low level of ARSB, genetic testing confirmed a diagnosis of Mucopolysaccharidosis type VI with a novel mutation in ARSB gene. There is a homozygous frameshift nonsense mutation by two thymine deletion in 770 and 771 codons (c. [770_771del TT]; [770_771del TT]). This is the first case and mutation of Mucopolysaccharidosis type VI detected in south Morocco. Keywords: : mucopolysaccharidosis VI; ARSB gene; nonsense mutation; ERT

Non-Allelic Homologous Recombination Leading to Premature Transcription Termination in the ARSB Gene as a Novel Cause of Mucopolysaccharidosis Type VI

Non-Allelic Homologous Recombination Leading to Premature Transcription Termination in the ARSB Gene as a Novel Cause of Mucopolysaccharidosis Type VI

A Child Presenting with Mucopolysaccharidosis

The lysosomal storage disorders are a group of diseases that are typified by an accumulation of waste products in the lysosomes. Mucopolysaccharidoses are lysosomal storage disorders due to diverse lysosomal enzyme deficiencies. Ms HT was 2 years and 5 months old when she presented to our metabolic bone clinic with clinical features that were suggestive of a genetic syndrome that was associated with a metabolic bone disease. The urine GAG spot test was positive. The MPS screen identified a reduction in arylsulfatase B activity and sequencing of the ARSB gene detected a pathogenic variant, in keeping with Maroteaux-Lamy syndrome. The diagnosis of MPS is confirmed by urine GAG, enzyme activity analysis and genetic testing. The available treatments include hematopoietic stem cell transplantation, enzyme replacement therapy and surgery. MPSs are heterogeneous, progressive, multisystem diseases for which diagnosis is often delayed. Greater awareness of MPS will enable early diagnosis and treatment. Treatment is however costly and is frequently unavailable to patients in the public sector.

Early Diagnosis and Results of Enzyme Replacement Therapy in the Patient with Mucopolysaccharidosis Type VI: Clinical Case

Background. Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is rare autosomal-recessive multisystem disease, one of the group of lysosomal storage diseases. The MPS VI pathogenesis is determined by arylsulfatase B enzyme deficiency caused by mutations in the ARSB gene. There are only few published clinical examples of this disease that covers the results of early enzyme replacement therapy (ERT) onset.Clinical case description. The child was suspected to have lysosomal storage disease at the age of 1.5 months, it was based on microscopic analysis of blood smears: Alder abnormality was revealed (granulations and red-violet inclusions in neutrophils, monocytes, lymphocytes cytoplasm). The diagnosis was confirmed at the age of 3 months: increased glycosaminoglycans (GAGs) concentration in the urine, arylsulfatase B activity decrease in dried blood spots, and pathogenic variant c.943C&gt;T (p. R315X) in the ARSB gene in homozygous state were revealed. ERT with galsulfase was started at the age of 7 months. There was decrease in excretion of GAGs in urine to normal level after 9 and 15 months of therapy. Normal growth and body proportions for the patient’s age were determined 3 years after continuous ERT. However, there was progression of multiple dysostosis and joint stiffness, as well as eyes lesion.Conclusion. Early ERT onset cannot completely stop MPS VI progression but it allows to reduce the severity of several symptoms and improves patient’s quality of life.