Morquio A syndrome
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- MeSH
- dítě MeSH
- genetika MeSH
- klinická chemie MeSH
- lidé MeSH
- mukopolysacharidóza IV genetika komplikace patologie MeSH
- riziko MeSH
- vývojové onemocnění kostí etiologie patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Hearing impairment is a prevalent clinical feature in Morquio syndrome (mucopolysaccharidosis IVA or MPS IVA) patients, often presenting in diverse forms: conductive, sensorineural, or a combination known as mixed hearing loss. The mixed form entails a blend of both conductive and sensorineural elements, typically exhibiting a progressive trajectory. This scoping review aimed to comprehensively analyze available evidence pertaining to the pathophysiology, classification, epidemiology, and clinical management of hearing loss in individuals with MPS IVA. METHODS: Targeted literature was searched using MEDLINE, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Web of Science, the Cochrane Library, Trip Medical Database, Embase, ScienceDirect, and Google Scholar, with a second search cycle to identify gray literature. A systematic search strategy using Medical Subject Headings keywords was implemented: "Hearing Disorders" OR "Hearing Loss" AND "Mucopolysaccharidosis IV" or "Hearing Disorders" OR "Hearing Loss" AND "Mucopolysaccharidosis IV." The identified bibliography was uploaded to COVIDENCE platform for information management. Articles were screened by 3 independent reviewers following the eligibility criteria. RESULTS: Twenty-seven articles met the inclusion criteria, spanning information from 568 patients across 16 different countries. None of the studies had complete epidemiological information. Only 2 studies provided sufficient data to address the pathophysiology, while 3 addressed management and treatment. Hearing loss was reported in 210 of 568 patients. A total of 19.2% of patients reported recurrent ear infections. None of the studies reported vertigo, tinnitus, or dizziness in the patients. Pure-tone audiometry was the primary test used to diagnose and monitor auditory impairment in patients with Morquio syndrome. CONCLUSIONS: Five hundred sixty-eight patients with MPS IVA were identified, of whom 210 (37%) developed hearing loss, the most common of which was moderate. Despite the lack of information on the diagnosis and management of hearing loss in Morquio syndrome, this study found that approximately one-third of participants exhibited some form of auditory impairment, with the majority of these cases being sensorineural in nature.
- MeSH
- lidé MeSH
- mukopolysacharidóza IV * komplikace epidemiologie diagnóza MeSH
- nedoslýchavost * epidemiologie diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- scoping review MeSH
BACKGROUND: The Morquio A Registry Study (MARS) is an ongoing, multinational, observational study of patients with MPS IVA. Key objectives of MARS are to characterize the heterogeneity and natural history of disease and to evaluate long-term effectiveness and safety of elosulfase alfa enzyme replacement therapy (ERT). Enrollment began in September 2014; data on medical history, clinical outcomes, and safety assessments are collected as part of routine care. RESULTS: As of February 2021, 381 subjects from 17 countries had enrolled in MARS: 58 ERT-naïve subjects and 323 ERT-treated subjects (≥1 infusion), with a mean ERT exposure of 5.5 years (SD 2.8) and median age at first ERT treatment of 9.8 years. ERT-treated subjects were younger at diagnosis (median 3.4 vs 6.5 years) relative to ERT-naïve subjects. Among ERT-treated subjects, urinary keratan sulfate (uKS) levels declined from pre-ERT baseline to last follow-up on treatment (mean % change [95% confidence interval]: -52.5% [-57.5%, -47.4%]; n = 115) and 6-min walk test distance remained stable (mean change: -6.1 [-27.6, 15.5] m; n = 131) over a mean follow-up of 5.5 years. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) increased in subjects who were < 18 years of age at ERT initiation (mean change: +0.3 [0.1, 0.4] L and + 0.4 [0.3, 0.5] L; mean follow-up: ∼6 years; n = 82) and were stable in subjects ≥18 years (mean change: 0.0 [-0.0, 0.1] L and 0.0 [-0.1, 0.1] L; mean follow-up: 4.6 years; n = 38). Overall, 148 (47.1%) ERT-treated subjects experienced ≥1 adverse event (AE) and 110 subjects (35%) reported ≥1 serious AE. Drug-related AEs were reported in 39 (12.4%) subjects; the most common were hypersensitivity (9 subjects [2.9%]), urticaria (8 subjects [2.5%]), and pyrexia (7 subjects [2.2%]). CONCLUSIONS: MARS is the longest and largest observational study of MPS IVA patients to date, with a heterogenous population that is representative of the MPS IVA population overall. Data collected over the first 6 years of MARS provide real-world evidence for long-term stabilization of endurance and respiratory function among ERT-treated patients, with no new safety concerns identified.
BACKGROUND: Mild to moderate hearing loss is common in patients with mucopolysaccharidosis (MPS) IVA. The hearing loss can be conductive, sensorineural, or mixed. However, in these patients, the mixed form is frequent, attributed to the combination of conductive and neurosensory elements, with slowly progressive evolution. Conductive hearing loss may be secondary to recurrent upper respiratory tract infections, serous otitis media, and deformities of the ear ossicles due to the accumulation of glycosaminoglycans (GAGs). Meanwhile, the sensorineural form is mainly attributed to the accumulation of GAGs in the auditory system. OBJECTIVE: The aim of this scoping review is to understand the extent and type of evidence in relation to the physiopathology, classification, epidemiology, and clinical management of hearing loss and the effect of therapy for hearing loss in patients with MPS IVA. METHODS: This scoping review includes participants across all genders and of no particular age group who are diagnosed with MPS IVA and develop hearing loss as a comorbidity. No exclusion criteria (country, language, or document type) will be applicable. The information sources will include experimental and quasi-experimental, analytical observational, observational, and qualitative studies. Unpublished literature will not be covered. Grey literature will be covered. A total of 2 independent reviewers will participate in the process of screening the literature, paper selection, and data extraction, and this process will be performed blindly. When all manuscripts have been selected, disagreements that arise between the 2 reviewers at each stage of the selection process will be resolved through discussion or with an additional reviewer. Results will be reported with descriptive statistics and information will be displayed in a diagrammatic or tabular manner, as explained in the JBI guidelines. RESULTS: The literature search was performed in November 2021 in MEDLINE, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), the Cochrane Library, ScienceDirect, Google Scholar, and OpenGrey; a total of 780 results were retrieved. Completion of the review is expected in mid-2022. CONCLUSIONS: This scoping review will be the first to describe the extent of the information regarding the development of hearing loss in the MPS IVA population. The data gathered by this review may lead to an understanding of the grade of hearing loss in this population and allow for the assessment of possible interventions according to the disease pattern. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32986.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries. Aim of this statement is to provide evidence-based guidance for the enzyme replacement treatment of Morquio A patients, harmonizing recommendations from published guidelines with the real-life clinical practice in the Central and South-Eastern European region. PARTICIPANTS: The Consensus Group, convened by 8 Steering Committee (SC) members from 7 Central and South-Eastern European countries, consisted of a multidisciplinary group of 17 experts in the management of MPS in Central and South-Eastern Europe. CONSENSUS PROCESS: The SC met in a first virtual meeting with an external scientific coordinator, to discuss on clinical issues to be analyzed in guidance statements. Statements were developed by the scientific coordinator, evaluated by the SC members in a first modified-Delphi voting and adapted accordingly, to be submitted to the widest audience in the Consensus Conference. Following discussion and further modifications, all participants contributed to a second round of modified-Delphi voting. RESULTS: Nine of ten statements, concerning general guidelines for management of MPS IVA patients and specific recommendations for treatment, received final consensus. CONCLUSIONS: European guidelines and evidence-based recommendations for Morquio A patients should be considered in the real life of Central and South-Eastern European countries and adapted to unique clinical practice approaches and criteria for patients' access to treatment and reimbursement in the region.
- MeSH
- enzymová substituční terapie MeSH
- isovaleryl-CoA-dehydrogenasa nedostatek MeSH
- konsensus MeSH
- lidé MeSH
- mukopolysacharidóza IV * farmakoterapie MeSH
- mukopolysacharidózy * farmakoterapie MeSH
- vrozené poruchy metabolismu aminokyselin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. RESULTS: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. CONCLUSIONS: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.
- MeSH
- dospělí MeSH
- enzymová substituční terapie metody MeSH
- kvalita života MeSH
- lidé MeSH
- mukopolysacharidóza II * farmakoterapie MeSH
- mukopolysacharidóza IV * farmakoterapie MeSH
- mukopolysacharidózy * farmakoterapie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- brodalumab,
- MeSH
- biologická terapie metody MeSH
- dospělí MeSH
- hidradenitis suppurativa * farmakoterapie komplikace patologie MeSH
- komorbidita MeSH
- lidé MeSH
- mukopolysacharidóza IV * komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- chemické jevy MeSH
- chemie MeSH
- diferenciální diagnóza MeSH
- glykosaminoglykany metabolismus MeSH
- lidé MeSH
- mentální retardace diagnóza komplikace MeSH
- mukopolysacharidóza IV diagnóza MeSH
- mukopolysacharidózy diagnóza komplikace MeSH
- pojivová tkáň metabolismus MeSH
- předškolní dítě MeSH
- retinopathia pigmentosa diagnóza komplikace MeSH
- vrozené poruchy metabolismu sacharidů diagnóza komplikace MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- MeSH
- akromegalie komplikace MeSH
- alkaptonurie komplikace MeSH
- biologické pigmenty MeSH
- dna (nemoc) komplikace MeSH
- hemochromatóza komplikace MeSH
- hemofilové infekce komplikace MeSH
- kolenní kloub MeSH
- kostní dřeň MeSH
- kyčelní kloub MeSH
- lidé MeSH
- loketní kloub MeSH
- mukopolysacharidóza IV komplikace MeSH
- nemoci chrupavky komplikace MeSH
- nemoci kloubů komplikace MeSH
- nemoci kostí komplikace MeSH
- obezita komplikace MeSH
- osteoartróza etiologie MeSH
- osteochondritida komplikace MeSH
- ramenní kloub MeSH
- revmatoidní artritida komplikace MeSH
- synoviální tekutina MeSH
- Check Tag
- lidé MeSH
