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1.
Cytokine ; 173: 156410, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37924740

RESUMO

Recently, it has been shown disturbances in oxidant/antioxidant system and increases in some inflammatory markers in animal studies and in some Mucopolysaccharidoses (MPSs) patients. In this study, we aimed to determine the oxidative stress/antioxidant parameters and pro-inflammatory cytokine levels in the serum of MPS patients, in order to evaluate the possible role of inflammation in these patient groups regarding to accumulated metabolites. MPS I (n = 3), MPS II (n = 8), MPS III (n = 4), MPS IVA (n = 3), MPS VI (n = 3), and VII (n = 1) patients and 20 age-matched healthy subjects were included into the study. There was no statistically significant change in activities of SOD, Catalase, GSH-Px and lipid peroxidation levels in erythrocytes between the MPS patients and healthy controls. While IL-1alpha (p = 0.054), IL-6 (p = 0.008) levels, and chitotriosidase activity (p = 0.003) elevated in MPS3 patients, IL1α (p = 0.006), IL-1ß (p = 0.006), IL-6 (p = 0.006), IFNγ (p = 0.006), and NFκB (p = 0.006) levels increased in MPS-6 patients. Elevated levels of IL-6, IL1α and chitotriosidase activity demonstrated macrophage activation in MPSIII untreated with enzyme replacement. Our study showed for the first time that high levels of IL1α, IL-6, IL1ß and NFκB were present in MPSVI patients, demonstrating the induction of inflammation by dermatan sulphate. The low level of paraoxonase in MPSVI patients may be a good marker for cardiac involvement. Overall, this study provides important insights into the relationship between lysosomal storage of glycosaminoglycan and inflammation in MPS patients. It highlights possible pathways for the increased release of inflammatory molecules and suggests new targets for the development of treatments.


Assuntos
Mucopolissacaridoses , Mucopolissacaridose VI , Animais , Humanos , Glicosaminoglicanos/metabolismo , Interleucina-6 , Antioxidantes , Mucopolissacaridoses/metabolismo , Inflamação
2.
Mol Genet Metab ; 141(1): 108105, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128203

RESUMO

Previously we developed a multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using dried blood spots for all subtypes of mucopolysaccharidoses (MPS) except MPS-IIID. Here we show that the MPS-IIID enzyme N-acetylglucosamine-6-sulfatase (GNS) is inhibited in dried blood spot (DBS) extracts, but activity can be recovered if the extract is diluted to reduce the concentrations of endogenous inhibitors. The new GNS assay displays acceptable characteristics including linearity in product formation with incubation time and amount of enzyme, low variability, and ability to distinguish MPS-IIID-affected from healthy patients using DBS. The assay can be added to the LC-MS/MS multiplex panel for all MPS subtypes requiring ∼2 min per newborn for the LC-MS/MS run.


Assuntos
Mucopolissacaridoses , Mucopolissacaridose VI , Recém-Nascido , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Sulfatases , Teste em Amostras de Sangue Seco/métodos
3.
Stem Cell Res ; 73: 103259, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38006675

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas , Mucopolissacaridose VI , Feminino , Humanos , Pré-Escolar , Células-Tronco Pluripotentes Induzidas/metabolismo , Mucopolissacaridose VI/metabolismo , Fator 4 Semelhante a Kruppel , Diferenciação Celular/genética , Fibroblastos/metabolismo , Reprogramação Celular
4.
Orphanet J Rare Dis ; 18(1): 338, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891668

RESUMO

BACKGROUND: The Italian Medicines Agency (AIFA) demands precise information on benefit/risk profile of home-based enzyme replacement therapy (ERT) for the treatment of patients with Pompe disease and Mucopolysaccharidosis type I (MPS I). This passage is necessary to obtain the authorization for ERT home therapy, even after the coronavirus disease-19 (COVID-19) pandemic period. This research intends to evaluate the safety, treatment satisfaction, and compliance of MPS I patients treated with laronidase (Aldurazyme®) and Pompe Disease patients treated with alglucosidase alfa (Myozyme®) in a homecare setting. RESULTS: We report herein an early interim analysis of the HomERT (Home infusions of ERT) study, a multicenter, non-interventional, double-cohort study that retrospectively analyzed 38 patients from 14 sites in Italy: cohort A (Pompe disease - 32 patients) and cohort B (MPS I - 6 patients). Among the selected patients who started home therapy before enrollment, the average number of missed home-based infusions was 0.7 (1.3) in cohort A and 3.8 (6.4) in cohort B with no return to the hospital setting. Irrespective of the treatment location, 3 prior ADRs per cohort were reported. The majority of patients preferred home-based infusions (cohort A: 96.9%; cohort B: 100%): the main reason was attributed to treatment convenience (cohort A: 81.3%; cohort B: 83.3%). Despite the underlying conditions, most patients self-evaluated their health as "good" (cohort A: 50%; cohort B: 83.3%). CONCLUSIONS: Evidence of favorable safety profile, improved treatment compliance and personal satisfaction validates the use of ERT with laronidase and alglucosidase alfa as a strong candidate for home therapy.


Assuntos
COVID-19 , Doença de Depósito de Glicogênio Tipo II , Mucopolissacaridose I , Mucopolissacaridose VI , Humanos , Terapia de Reposição de Enzimas/efeitos adversos , Mucopolissacaridose I/tratamento farmacológico , Estudos de Coortes , Estudos Retrospectivos , Preferência do Paciente , alfa-Glucosidases
5.
JCI Insight ; 8(21)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37751300

RESUMO

Mucopolysaccharidosis VI (MPS VI) is a rare lysosomal disease arising from impaired function of the enzyme arylsulfatase B (ARSB). This impairment causes aberrant accumulation of dermatan sulfate, a glycosaminoglycan (GAG) abundant in cartilage. While clinical severity varies along with age at first symptom manifestation, MPS VI usually presents early and strongly affects the skeleton. Current enzyme replacement therapy (ERT) does not provide effective treatment for the skeletal manifestations of MPS VI. This lack of efficacy may be due to an inability of ERT to reach affected cells or to the irreversibility of the disease. To address the question of reversibility of skeletal phenotypes, we generated a conditional by inversion (COIN) mouse model of MPS VI, ArsbCOIN/COIN, wherein Arsb is initially null and can be restored to WT using Cre. We restored Arsb at different times during postnatal development, using a tamoxifen-dependent global Cre driver. By restoring Arsb at P7, P21, and P56-P70, we determined that skeletal phenotypes can be fully rescued if Arsb restoration occurs at P7, while only achieving partial rescue at P21 and no significant rescue at P56-P70. This work has highlighted the importance of early intervention in patients with MPS VI to maximize therapeutic impact.


Assuntos
Mucopolissacaridose VI , N-Acetilgalactosamina-4-Sulfatase , Camundongos , Animais , Humanos , Mucopolissacaridose VI/tratamento farmacológico , Mucopolissacaridose VI/diagnóstico , N-Acetilgalactosamina-4-Sulfatase/genética , N-Acetilgalactosamina-4-Sulfatase/uso terapêutico , Fenótipo , Glicosaminoglicanos , Esqueleto
6.
Nanoscale ; 15(21): 9348-9364, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37165691

RESUMO

Enzyme replacement therapy shows remarkable clinical improvement in treating lysosomal storage disorders. However, this therapeutic approach is hampered by limitations in the delivery of the enzyme to cells and tissues. Therefore, there is an urgent, unmet clinical need to develop new strategies to enhance the enzyme delivery to diseased cells. Graphene-based materials, due to their dimensionality and favourable pattern of interaction with cells, represent a promising platform for the loading and delivery of therapeutic cargo. Herein, the potential use of graphene-based materials, including defect-free graphene with positive or negative surface charge and graphene oxide with different lateral dimensions, was investigated for the delivery of lysosomal enzymes in fibroblasts derived from patients with Mucopolysaccharidosis VI and Pompe disease. We report excellent biocompatibility of all graphene-based materials up to a concentration of 100 µg mL-1 in the cell lines studied. In addition, a noticeable difference in the uptake profile of the materials was observed. Neither type of graphene oxide was taken up by the cells to a significant extent. In contrast, the two types of graphene were efficiently taken up, localizing in the lysosomes. Furthermore, we demonstrate that cationic graphene flakes can be used as carriers for arylsulfatase B enzyme, for the delivery of the lacking enzyme to the lysosomes of Mucopolysaccharidosis VI fibroblasts. Arylsulfatase B complexed with cationic graphene flakes not only retained the enzymatic activity, but also exerted biological effects almost twice as high as arylsulfatase B alone in the clearance of the substrate in Mucopolysaccharidosis VI fibroblasts. This study lays the groundwork for the potential use of graphene-based materials as carriers for enzyme replacement therapy in lysosomal storage disorders.


Assuntos
Grafite , Mucopolissacaridose VI , N-Acetilgalactosamina-4-Sulfatase , Humanos , Grafite/metabolismo , N-Acetilgalactosamina-4-Sulfatase/metabolismo , Mucopolissacaridose VI/metabolismo , Fibroblastos , Lisossomos/metabolismo
8.
J Inherit Metab Dis ; 46(4): 695-704, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36840680

RESUMO

The mucopolysaccharidosis (MPS) disorders have many potential new therapies on the horizon. Thus, historic control data on disease progression and variability are urgently needed. We conducted a 10-year prospective observational study of 55 children with MPS IH (N = 23), MPS IA (N = 10), non-neuronopathic MPS II (N = 13), and MPS VI (N = 9) to systematically evaluate bone and joint disease. Annual measurements included height, weight, and goniometry. Mixed effects modeling was used to evaluate changes over time. All participants had been treated with hematopoietic cell transplantation and/or enzyme replacement therapy. Height z-score decreased over time in MPS IH, MPS II, and MPS VI, but not MPS IA. Adult heights were 136 ± 10 cm in MPS IH, 161 ± 11 cm in MPS IA, 161 ± 14 cm in MPS II, and 128 ± 15 cm in MPS VI. Adult average BMI percentiles were high: 75 ± 30%ile in MPS IH, 71 ± 37%ile in MPS IA, 71 ± 25%ile in MPS II, and 60 ± 42%ile in MPS VI. Every participant had joint contractures of the shoulders, elbows, hips, and/or knees. Joint contractures remained stable over time. In conclusion, despite current treatments for MPS I, II, and VI, short stature and joint contractures persist. The elevation in average BMI may be related, in part, to physical inactivity due to the ongoing bone and joint disease. Data from this longitudinal historical control study may be used to expedite testing of experimental bone and joint directed therapies and to highlight the need for weight management as part of routine clinical care for patients with MPS.


Assuntos
Contratura , Artropatias , Mucopolissacaridoses , Mucopolissacaridose II , Mucopolissacaridose I , Mucopolissacaridose VI , Criança , Adulto , Humanos , Estudos Prospectivos , Mucopolissacaridose I/tratamento farmacológico , Mucopolissacaridoses/terapia , Mucopolissacaridose VI/tratamento farmacológico , Mucopolissacaridose II/tratamento farmacológico
9.
Minerva Pediatr (Torino) ; 75(2): 243-252, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-32748606

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Mucopolissacaridose VI , N-Acetilgalactosamina-4-Sulfatase , Humanos , Idade de Início , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/genética , N-Acetilgalactosamina-4-Sulfatase/química , N-Acetilgalactosamina-4-Sulfatase/genética , Mutação , Fenótipo
10.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 63-69, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36495517

RESUMO

Mucopolysaccharidoses type VI is a rare disorder and establishing the diagnosis requires assays that are unavailable in a routine care setting. There is an increased risk of considerable diagnostic delay and missing patients due to incorrect diagnosis. The present study was conducted to determine the socio-demographic characteristics, clinical manifestations, and anthropometric parameters of patients with MPS type VI. Patients' enzyme levels and genetic profiles were also examined. The present study included a total of 16 patients who had been diagnosed as MPS type VI and were referred to Hivi Pediatric Hospital in Duhok, Kurdistan Region, Iraq, till the time period of March 2022. Diagnoses were made in all the patients by analyzing the enzyme level. Moreover, a genetic study was performed to confirm the diagnosis. From each of the patients, a blood sample was taken to determine the hematological parameters. Among the study participants, 9 were males and 7 were females. The mean age of the patients was 6.81±4.99 years and the age at diagnosis was 21.13±15.19 months. All of them presented with a course facial features, 75% had short stature, 87.5% had corneal clouding, 12.5%  had glaucoma, 68.75% had poor vision, 18.75% of them had optic nerve disease, 56.25% had otitis media, 56.25% had poor hearing, 68.75% had a history of recurrent sinusitis, 50% had an enlarged tongue, and 75% had abnormal teeth. Approximately 56.25% of the patients presented with sleep apnea, 37.5% had obstructive and restrictive airway disease, none of the patients had cardiac arrhythmia, 37.5% had cardiomyopathy, 31.25% had abdominal hepatosplenomegaly, 81.25% had skeletal abnormalities, all of the patients had normal intelligence, 9 (56.25%) had a past medical history of other systemic illness and 7 (43.75%) had a past history of surgery. Out of the total number of patients, 13 patients had c.962T>C (p.(Leu321Pro)) mutation, one patient had c.585T>A (p.(ASP195Glu)) mutation, one patient had c.[585T>A];[753C>G] (Asp195 Glu];[Tyr251 Ter]), and one patient had c.{288C>A];[962T>C]   (p.[Ser96Arg];[Leu321Pro]) mutations. Due to the rarity in prevalence, early detection of the said disorder is critical; early treatment may result in improved outcomes, which may have potential significance for newborn screening.


Assuntos
Diagnóstico Tardio , Mucopolissacaridose VI , Criança , Masculino , Feminino , Recém-Nascido , Humanos , Lactente , Pré-Escolar , Mucopolissacaridose VI/diagnóstico , Mutação , Iraque/epidemiologia
11.
Int J Mol Sci ; 23(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36361933

RESUMO

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.


Assuntos
Mucopolissacaridose VI , N-Acetilgalactosamina-4-Sulfatase , Humanos , Sulfatos de Condroitina/metabolismo , Dermatan Sulfato , Mucopolissacaridose VI/genética , Mucopolissacaridose VI/metabolismo , N-Acetilgalactosamina-4-Sulfatase/genética , N-Acetilgalactosamina-4-Sulfatase/metabolismo , Sulfatos
12.
Diagn Interv Radiol ; 28(5): 516-521, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36218154

RESUMO

PURPOSE lthough clinical ophthalmologic findings have been reported, no study documented magnetic resonance imaging (MRI) findings in mucopolysaccharidosis (MPS) type VI. The aim of this study was to determine the ophthalmologic imaging findings of MPS type VI in the pediatric age group retrospectively. METHODS Brain MRIs of 10 patients with MPS type VI and 49 healthy children were evaluated independently by two pediatric radiologists for the following characteristics: globe volume, ocular wall thickness, and optic nerve sheath diameter for each orbit. The means of the measurement of each group were compared by using an independent t-test. Agreement and bias between reviewers were assessed by intra-class correlation coefficients (ICC). RESULTS A total of 59 children [32 girls (54.23%), 27 boys (45.77%); age range, 4-16 years; mean age, 10.37 ± 3.73 years] were included in the study. Statistical analysis revealed smaller eyeballs and thicker ocular walls of patients with MPS type VI (P < .001 and P < .001, respectively). However, there was no statistically significant difference in terms of optic nerve sheath diameter between the two groups (P=.648). CONCLUSION Patients with MPS type VI displayed reduced globe volumes and increased ocular wall thicknesses compared to the healthy children. Therefore, we recommend that ophthalmologic imaging findings might prove to be an auxiliary tool in the diagnosis of MPS patients.


Assuntos
Mucopolissacaridose VI , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/patologia , Estudos Retrospectivos
13.
Orphanet J Rare Dis ; 17(1): 339, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064607

RESUMO

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficient activity of enzymes responsible for the catabolism of glycosaminoglycans (GAGs), resulting in progressive damage to various tissues and organs. Affected individuals present with skeletal deformities, bone growth impairment, joint stiffness and frequently mental retardation. RESULTS: The objective of the study was to summarise over 30 years of observations of the growth dynamics in patients with different types of MPS, performed at the Children's Memorial Health Institute (CMHI, Warsaw, Poland). A retrospective analysis of anthropometric data collected from 1989 to 2020 was performed for 195 patients with MPS I, MPS II, MPS III, MPS IVA and MPS VI. Mean values for birth body length were statistically significantly greater than in the general population. The mean z-scores for other MPS groups showed that until the 24th month of life, the growth pattern for all patients was similar, and the average z-scores for body height were greater than in reference charts. Afterwards, growth patterns began to differentiate for MPS groups. CONCLUSIONS: The long-term follow up showed that the growth pattern in patients with all types of mucopolysaccharidoses significantly deviates from the general population. Patients with MPS IVA had the most severe growth impairments compared to other patients in the study group. Neuropathic MPS I and II demonstrated severe growth impairments compared to other patients in this study. Patients with MPS III showed the mildest growth impairments compared to other MPS patients and reached the 3rd percentile last.


Assuntos
Mucopolissacaridoses , Mucopolissacaridose III , Mucopolissacaridose IV , Mucopolissacaridose I , Mucopolissacaridose VI , Criança , Humanos , Estudos Retrospectivos
15.
Ophthalmic Genet ; 43(5): 693-698, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35658818

RESUMO

PURPOSE: To describe and compare the systemic and ocular findings in two siblings with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome), one treated with recombinant galsulfase, and one who was untreated. METHOD: One female patient aged 33 years (case 1) who had received galsulfase enzyme replacement therapy for 11 years, and her younger male sibling by 3 years (case 2), who had declined systemic treatment, underwent clinical ophthalmic examination and retinal ocular coherence tomography. The female sibling underwent electrophysiology testing of visual function. RESULTS: Case 1 had best corrected visual acuity right 6/4.8 and left 6/6. Case 2 had best corrected visual acuity of 6/6 in each eye. Case 1 had bilateral mild corneal haze and a clinically unremarkable posterior segment examination. Case 2 had bilateral very mild corneal haze and retinal striae on examination. Ocular coherence tomography showed choroidal folds at the maculae in both patients, more pronounced in Case 2, who also had retinal folds and epiretinal membrane. Electroretinography showed very mild involvement of the rods only in Case 1. CONCLUSION: These two siblings with mucopolysaccharidosis type VI, one treated and one untreated, displayed variable levels of systemic, corneal, and chorioretinal involvement in their disease Further studies of choroidal changes in MPS VI may prove useful as a biomarker of ocular response to treatment outside the blood-retina barrier. Both patients have provided written consent to publish case details.


Assuntos
Opacidade da Córnea , Mucopolissacaridose VI , Córnea , Terapia de Reposição de Enzimas/métodos , Feminino , Humanos , Masculino , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/tratamento farmacológico , Irmãos
16.
Orphanet J Rare Dis ; 17(1): 251, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768874

RESUMO

BACKGROUND: Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by the deficit of lysosomal hydrolases involved in the degradation of glycosaminoglycans (GAGs). The course is chronic and progressive, with multisystemic involvement that often leads to cardiovascular disease. We describe the overall incidence and type of cardiac damage in a cohort of Italian MPS patients, and their progression over time, also with reference to treatment efficacy in patients under Enzyme Replacement Therapy (ERT). Moreover, we report a possible association between genetic variants and cardiac phenotype in homozygous and hemizygous patients to understand whether a more aggressive clinical phenotype would predict a greater cardiac damage. RESULTS: Our findings confirm that cardiac involvement is very common, already at diagnosis, in MPS VI (85.7% of our cohort), and in MPS II (68% of our cohort) followed by MPS I subjects (55% of our cohort). The most frequent heart defect observed in each MPS and at any time-point of evaluation was mitral insufficiency; 37% of our patients had mitral insufficiency already at diagnosis, and 60% at post-ERT follow-up. After at least six years of treatment, we observed in some cases (including 6 MPS II, 2 MPS IV and 2 MPS VI) a total regression or improvement of some signs of the cardiac pathology, including some valve defects, though excluding aortic insufficiency, the only valvulopathy for which no regression was found despite ERT. The general clinical phenotype proved not to be strictly correlated with the cardiac one, in fact in some cases patients with an attenuated phenotype developed more severe heart damage than patients with severe phenotype. CONCLUSIONS: In conclusion, our analysis confirms the wide presence of cardiopathies, at different extent, in the MPS population. Since cardiac pathology is the main cause of death in many MPS subtypes, it is necessary to raise awareness among cardiologists about early cardiac morpho-structural abnormalities. The encouraging data regarding the long-term effects of ERT, also on heart damage, underlines the importance of an early diagnosis and timely start of ERT.


Assuntos
Traumatismos Cardíacos , Insuficiência da Valva Mitral , Mucopolissacaridoses , Mucopolissacaridose II , Mucopolissacaridose VI , Terapia de Reposição de Enzimas , Traumatismos Cardíacos/tratamento farmacológico , Humanos , Incidência , Insuficiência da Valva Mitral/tratamento farmacológico , Mucopolissacaridoses/tratamento farmacológico , Mucopolissacaridose II/tratamento farmacológico , Mucopolissacaridose VI/tratamento farmacológico
17.
J Med Life ; 15(4): 579-586, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35646169

RESUMO

Mucopolysaccharidosis VI is a genetic disorder affecting multiple organs with sundry clinical presentations. The main etiological factor reflects the disturbances in mucopolysaccharide metabolism leading to deposition of acid mucopolysaccharide in various tissues. The pathognomonic features of the disease include a large head, short neck, corneal opacity, open mouth associated with an enlarged tongue, enlargement of the skull, and long anteroposterior dimension with unerupted dentition, dentigerous cyst-like follicles, condylar defects, and gingival hyperplasia. An 18-year-old boy with Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is described in this article, emphasizing the oral manifestations and radiographic illustration of lesions in the jaws. It also emphasizes the essential role of cone-beam computed tomography to identify and analyze multicentric pathologies in the jaws.


Assuntos
Cisto Dentígero , Macroglossia , Mucopolissacaridose VI , Tomografia Computadorizada de Feixe Cônico Espiral , Adolescente , Cisto Dentígero/complicações , Cisto Dentígero/diagnóstico por imagem , Glicosaminoglicanos , Humanos , Macroglossia/complicações , Masculino , Mucopolissacaridose VI/complicações , Mucopolissacaridose VI/diagnóstico por imagem , Mucopolissacaridose VI/patologia
18.
Eur Spine J ; 31(7): 1693-1699, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35267074

RESUMO

PURPOSE: Spinal abnormalities frequently occur in patients with mucopolysaccharidosis (MPS) types I, II, IV, and VI. The symptoms are manifold, which sometimes prolongs the diagnostic process and delays therapy. Spinal stenosis (SS) with spinal cord compression due to bone malformations and an accumulation of storage material in soft tissue are serious complications of MPS disease. Data on optimal perioperative therapeutic care of SS is limited. METHODS: A retrospective chart analysis of patients with MPS and SS for the time period 01/1998 to 03/2021 was performed. Demographics, clinical data, neurological status, diagnostic evaluations (radiography, MRI, electrophysiology), and treatment modalities were documented. The extent of the SS and spinal canal diameter were analyzed. A Cox regression analysis was performed to identify prognostic factors for neurological outcomes. RESULTS: Out of 209 MPS patients, 15 were included in this study. The most dominant type of MPS was I (-H) (n = 7; 46.7%). Preoperative neurological deterioration was the most frequent indication for further diagnostics (n = 12; 80%). The surgical procedure of choice was dorsal instrumentation with microsurgical decompression (n = 14; 93.3%). A univariate Cox regression analysis showed MPS type I (-H) to be associated with favorable neurological outcomes. CONCLUSION: Early detection of spinal stenosis is highly relevant in patients with MPS. Detailed neurological assessment during follow-up is crucial for timeous detection of patients at risk. The surgical intervention of choice is dorsal instrumentation with microsurgical decompression and resection of thickened intraspinal tissue. Patients with MPS type I (-H) demonstrated the best neurological course.


Assuntos
Mucopolissacaridoses , Mucopolissacaridose VI , Compressão da Medula Espinal , Estenose Espinal , Descompressão Cirúrgica/efeitos adversos , Humanos , Mucopolissacaridoses/complicações , Mucopolissacaridoses/cirurgia , Mucopolissacaridose VI/complicações , Mucopolissacaridose VI/tratamento farmacológico , Mucopolissacaridose VI/cirurgia , Estudos Retrospectivos , Medula Espinal/cirurgia , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Estenose Espinal/complicações , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia
19.
Orphanet J Rare Dis ; 17(1): 91, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236367

RESUMO

BACKGROUND: Patients are the most important stakeholders in the care of any disease and have an educational need to learn about their condition and the treatment they should receive. Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. Independent guidelines on the treatment of these diseases were recently published, providing evidence- and expertise-driven recommendations to optimize patient management. However, while healthcare providers may have the training and knowledge to understand these guidelines, patients and their caregivers can find the technical content challenging. Hence, we aimed to develop plain language summaries (PLS) of the MPS VI and MPS IVA guidelines with patients as the primary audience. RESULTS: A review of the guidelines by an expert team identified six domains of information relevant to patients: The multidisciplinary team, regular tests and check-ups, disease-modifying and supportive treatments, general anesthetics, ear-nose-throat/respiratory care, and surgeries. This information was adapted into a series of infographics specific to either MPS VI or MPS IVA, designed to appeal to patients and clearly present information in a concise manner. CONCLUSIONS: The use of patient-friendly materials, like the infographics we have developed, has the potential to better inform patients and engage them in their care. We issue a "call to arms" to the medical community for the development of similar PLS materials in rare diseases intended to inform and empower patients.


Assuntos
Mucopolissacaridose IV , Mucopolissacaridose VI , Humanos , Educação de Pacientes como Assunto
20.
J Med Case Rep ; 16(1): 46, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078524

RESUMO

BACKGROUND: Mucopolysaccharidosis VI, or Maroteaux-Lamy disease, is an autosomal recessive disease characterized by deficiency of the enzyme arylsulfatase B in the lysosomal catabolism of glycosaminoglycans. Due to reduced (or even null) enzyme activity, glycosaminoglycans (mainly dermatan sulfate) accumulates, leading to a multisystemic disease. Mucopolysaccharidosis VI induces reduced growth, coarse face, audiovisual deficits, osteoarticular deformities, and cardiorespiratory issues, hampering the quality of life of the patient. Enzyme replacement therapy with galsulfase (Naglazyme, BioMarin Pharmaceuticals Inc., USA) is the specific treatment for this condition. Although studies have shown that enzyme replacement therapy slows the progression of the disease, the effects of long-term enzyme replacement therapy remain poorly understood. CASE PRESENTATION: A 29-year-old, Caucasian, male patient diagnosed with mucopolysaccharidosis VI was treated with enzyme replacement therapy for over 15 years. Enzyme replacement therapy was initiated when patient was 13 years old. The patient evolved multiplex dysostosis, carpal tunnel syndrome, thickened mitral valve, and hearing and visual loss. CONCLUSIONS: Although enzyme replacement therapy did not prevent the main signs of mucopolysaccharidosis VI, it slowed their progression. Additionally, enzyme replacement therapy was associated with a longer survival compared with the untreated affected sibling. Taken together, the results indicate that enzyme replacement therapy positively modified the course of the disease.


Assuntos
Síndrome do Túnel Carpal , Mucopolissacaridose VI , Adolescente , Adulto , Terapia de Reposição de Enzimas , Glicosaminoglicanos/uso terapêutico , Humanos , Masculino , Mucopolissacaridose VI/tratamento farmacológico , Qualidade de Vida
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