RESUMO
Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive inherited lysosomal storage disease. With pathogenic variants of the IDS gene, the activity of iduronate-2-sulfatase (IDS) is reduced or lost, causing the inability to degrade glycosaminoglycans (GAGs) in cells and influencing cell function, eventually resulting in multisystemic manifestations, such as a coarse face, dysostosis multiplex, recurrent respiratory tract infections, and hernias. Diagnosing MPS II requires a combination of clinical manifestations, imaging examinations, urinary GAGs screening, enzyme activity, and genetic testing. Currently, symptomatic treatment is the main therapeutic approach. Owing to economic and drug availability issues, only a minority of patients opt for enzyme replacement therapy or hematopoietic stem cell transplantation. The limited awareness of the disease, the lack of widespread detection technology, and uneven economic development contribute to the high rates of misdiagnosis and missed diagnosis in China.
Assuntos
Mucopolissacaridose II , Humanos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/terapia , Terapia de Reposição de Enzimas , Transplante de Células-Tronco Hematopoéticas , Testes Genéticos , Iduronato Sulfatase/uso terapêuticoRESUMO
PURPOSE: To report clinical and imaging features of optic nerve and retinal involvement in a patient with mucopolysaccharidosis (MPS) type II B. METHODS: A 27-year-old man, diagnosed with MPS type II B and undergoing enzymatic substitution therapy for the past 19 years, was referred to the retina service. An ophthalmological evaluation, which included multimodal imaging, was conducted to investigate potential retinal and optic disc involvement. RESULTS: The eye examination revealed a pigmentary retinopathy with a predominant loss of the outer retinal loss, primarily in the parafoveal and perifoveal regions. Notably, multimodal imaging identified macular edema without any signs of leakage, implying an association between macular edema and retinal neurodegeneration. Additionally, both eyes exhibited an optic disc with blurred margins. CONCLUSION: We herein describe the multimodal imaging findings of retinal and optic disc involvement in a patient with MPS type II B. This report describes for the first-time the presence of macular edema without leakage alongside photoreceptor damage and optic disc swelling.
Assuntos
Angiofluoresceinografia , Edema Macular , Mucopolissacaridose II , Disco Óptico , Papiledema , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Masculino , Adulto , Edema Macular/diagnóstico , Edema Macular/etiologia , Papiledema/diagnóstico , Papiledema/etiologia , Angiofluoresceinografia/métodos , Disco Óptico/patologia , Disco Óptico/diagnóstico por imagem , Mucopolissacaridose II/complicações , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/tratamento farmacológico , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/complicações , Imagem Multimodal , Fundo de OlhoRESUMO
Mucopolysaccharidoses are a group of rare lysosomal accumulation diseases caused by a deficiency of the lysosomal enzyme and the accumulation of mucopolysaccharides in various organs and tissues. Children with mucopolysaccharidosis type II (Hunter syndrome) develop multisystem dysfunction, including severe airway obstruction. At the same time, 34% of patients already at an early age (2-3 years) undergo surgical manipulations related to ENT organs (tonsillectomy, adenotomy). The article describes a clinical case of diagnosis of type II mucopolysaccharidosis by a pediatric otorhinolaryngologist. The main manifestations of the disease are discussed in detail, including the presence of indications for adenotomy at the age of 2 years, episodes of otitis media, which served as diagnostic markers for suspected orphan disease mucopolysaccharidosis type II. The leading role of the pediatric otorhinolaryngologist in the early diagnosis of the rare disease mucopolysaccharidosis type II is substantiated.
Assuntos
Mucopolissacaridose II , Otite Média , Criança , Pré-Escolar , Glicosaminoglicanos , Humanos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/cirurgiaRESUMO
BACKGROUND: Mucopolysaccharidosis (MPS) refers to a group of lysosomal storage disorders for which seven types and 11 subtypes are currently recognized. Targeted next-generation sequencing (NGS) offers an important method of disease typing, diagnosis, prenatal diagnosis, and treatment. METHODS: Gene variations in 48 Chinese MPS patients were evaluated using NGS, and the pathogenicity of the DNA alterations was evaluated using PolyPhen2, SIFT, and Mutation Taster. The effect of amino acid substitution on protein structure was also assessed. RESULTS: Four pedigrees with MPS I (8.3%), 28 with MPS II (58.3%), two with MPS IIIA (4.2%), two with MPS IIIB (4.2%), six with MPS IVA (12.5%), one with MPS IVB (2.1%), and five with MPS VI (10.4%) were identified. Of the 69 variations identified, 11 were novel variants (three in IDUA, five in IDS, and three in GALNS), all of which were predicted to be disease-causing except for one, and were associated with impaired protein structure and function. CONCLUSIONS: Targeted NGS technology is effective for the gene-based testing of MPS disorders, which show high allelic heterogeneity. MPS II was the predominant form in Chinese. Our study expands the existing variation spectrum of MPS, which is important for disease management and genetic counseling.
Assuntos
Condroitina Sulfatases , Mucopolissacaridose II , Povo Asiático/genética , China , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/genética , LinhagemRESUMO
Hunter Syndrome is a genetic disease characterized by deficiency of Iduronate-2-Sulfatase enzyme activity, resulting in accumulation of glycoaminoglycans in various organs including the central airways. We report a case of severe tracheomalacia and airway stenosis at Hospital Sultanah Aminah, Johor Bahru, Malaysia requiring mechanical ventilation in a middle aged gentleman who was previously undiagnosed of mucopolysaccharidosis. The patient underwent emergency tracheostomy for failed intubation, when he presented with shortness of breath and acute respiratory failure. A contrast-enhanced computed tomography of the neck and thorax revealed that the trachea distal to the tracheostomy tube had collapsed with narrowed right and left main bronchus. These findings were confirmed via direct visualization of the airway through a flexible bronchoscopy. Eventually, a tracheal stenting were performed to maintain the airway patency and assist in weaning off from mechanical ventilation. Further investigations to identify the aetiology of the central airway stenosis revealed elevated urinary glycoaminoglycans and the absence of iduronate-2-Sulfatase activity tested on dried blood spots, thus confirming the diagnosis of Hunter Syndrome. Managing mucopolysacharidosis with central airway obstruction requires multidisciplinary team effort in handling the difficult airway, anaesthesiology risk, potential comorbidities and providing genetic counselling.
Assuntos
Obstrução das Vias Respiratórias , Mucopolissacaridose II , Traqueomalácia , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Broncoscopia , Constrição Patológica , Humanos , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose II/complicações , Mucopolissacaridose II/diagnóstico , Traqueomalácia/diagnóstico por imagem , Traqueomalácia/etiologia , TraqueostomiaRESUMO
BACKGROUND: Lysosomal Storage Diseases (LSD) are rare and multisytemic diseases which are caused by lysosomal enzyme deficiencies leading into accumulation of waste products due to an interruption in the decomposition process. Due to the low prevalence and therefore limited disease awareness as well as the fact that LSD patients present with unspecific symptoms the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between onset of symptoms and final diagnosis regarding e.g. self-perceived health, symptom burden and false diagnoses for patients with selected LSDs (Fabry disease (FD), Gaucher disease (GD) and Mucopolysaccharidosis type II (MPS II). METHODS: The study was conducted as a telephone based cross-sectional survey. All patients living in Germany with a confirmed diagnosis of FD, GD or MPS II were eligible to participate. The questionnaire was provided in advance in order to enable the participants to prepare for the interview. Only descriptive analyses were carried out. Single analyses were not carried out for all three patient groups due low case numbers. RESULTS: Of the overall population, 39 patients have been diagnosed with FD, 19 with GD and 11 with MPS II with the majority of patients being index patients. The majority of FD patients reported their current health status as "satisfactory" or better (79.5%). Self-perceived health status was observed to be at least stable or improving for the majority of FD patients compared to the year prior to diagnosis. The most frequently reported symptoms for patients with FD were paraesthesias (51.3%), whereas patients with GD reported a tendency for bleeding, blue spots or coagulation disorder (63.2%) as well as hepatomegaly and/or splenomegaly (63.2%) as the most commonly appearing symptoms. The number of patients reporting misdiagnoses was n = 5 (13.5%) for patients with FD and n = 5 (27.8%) for patients with GD. The median duration of the diagnostic delay was 21.0 years for FD, 20.0 years for GD and 2.0 years for MPS II. CONCLUSIONS: This study showed that self-perceived status of health for patients might improve once the final correct diagnoses has been made and specific treatment was available. Furthermore, it was observed that diagnostic delay is still high in Germany for a relevant proportion of affected patients. Further challenges in the future will still be to increase awareness for these diseases across the entire healthcare sector to minimize the diagnostic delay.
Assuntos
Diagnóstico Tardio/prevenção & controle , Doenças por Armazenamento dos Lisossomos/diagnóstico , Tempo para o Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Diagnóstico Tardio/tendências , Doença de Fabry/diagnóstico , Feminino , Doença de Gaucher/diagnóstico , Alemanha/epidemiologia , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose II/diagnóstico , Inquéritos e Questionários , Tempo para o Tratamento/tendênciasRESUMO
Lysosomal storage diseases (LSD) comprise a rare and heterogeneous group of nearly 50 heritable metabolic disorders caused by mutations in proteins critical for cellular lysosomal function. Defects in the activity of these proteins in multiple organs leads to progressive intra-lysosomal accumulation of specific substrates, resulting in disruption of cellular functions, extracellular inflammatory responses, tissue damage and organ dysfunction. The classification and clinical presentation of different LSD are dependent on the type of accumulated substrate. Some clinical signs and symptoms are common across multiple LSD, while others are more specific to a particular syndrome. Due to the rarity and wide clinical diversity of LSD, identification and diagnosis can be challenging, and in many cases diagnosis is delayed for months or years. Treatments, such as enzyme replacement therapy, haemopoietic stem cell transplantation and substrate reduction therapy, are now available for some of the LSD. For maximum effect, therapy must be initiated prior to the occurrence of irreversible tissue damage, highlighting the importance of prompt diagnosis. Herein, we discuss the clinical presentation, diagnosis and treatment of four of the treatable LSD: Gaucher disease, Fabry disease, Pompe disease, and two of the mucopolysaccharidoses (I and II). For each disease, we present illustrative case studies to help increase awareness of their clinical presentation and possible treatment outcomes.
Assuntos
Terapia de Reposição de Enzimas , Doença de Fabry/terapia , Doença de Gaucher/terapia , Doença de Depósito de Glicogênio Tipo II/terapia , Doenças por Armazenamento dos Lisossomos/terapia , Mucopolissacaridose II/terapia , Mucopolissacaridose I/terapia , Adulto , Pré-Escolar , Doença de Fabry/diagnóstico , Feminino , Doença de Gaucher/diagnóstico , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Humanos , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Masculino , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose II/diagnósticoRESUMO
OBJECTIVES: The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction. METHODS: A single-centre retrospective chart review of 61 patients (36 M/25F) with different MPS subtypes (MPS I (n = 15), MPS II (n = 10), MPS III (n = 17), MPS IV (n = 15) and MPS VI (n = 4)) was conducted. The age of ENT presentation and frequency of ENT symptoms, surgeries and their distribution among MPS subtypes was studied. The relationship between ENT presentation, first ENT surgery and the age of diagnosis was also evaluated. RESULTS: Median age at the first ENT manifestation was 2.8 years, median age at MPS diagnosis 4.1 years. The great majority of patients (90%) manifested at least one ENT diagnosis; often before the diagnosis of MPS (75%). Chronic/recurrent rhinosinusitis was the most prevalent ENT diagnosis (77%), followed by upper airway obstruction (65%) and hearing loss (53%). Chronic/recurrent rhinosinusitis was the first ENT symptom to appear (median age 2.2 years), followed by otitis media with effusion (3.7 years) and hearing loss (4.5 years). At least one ENT surgery was performed in 57% of patients; in 69% before MPS diagnosis was established. Median age of the first ENT surgery was 4.1 years. ENT symptoms and surgical procedures were earliest present in MPS II. CONCLUSIONS: Our study documents high and early occurrence of various otolaryngologic symptoms in MPS and thus highlights the role of ENT specialist in prompt diagnosis of these rare diseases and their long-term management.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Perda Auditiva/etiologia , Mucopolissacaridoses/complicações , Rinite/etiologia , Sinusite/etiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Mucopolissacaridoses/diagnóstico , Mucopolissacaridose I/complicações , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose II/complicações , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose III/complicações , Mucopolissacaridose III/diagnóstico , Mucopolissacaridose IV/complicações , Mucopolissacaridose IV/diagnóstico , Mucopolissacaridose VI/complicações , Mucopolissacaridose VI/diagnóstico , Otite Média com Derrame/etiologia , Procedimentos Cirúrgicos Otorrinolaringológicos , Estudos Retrospectivos , Adulto JovemRESUMO
A 60-year-old man presented with a 10-month history of of stereotypical spells characterized by vertigo, tinnitus, blurred vision, left hemibody numbness, and occasional syncope, precipitated by turning his head leftwards. Cerebral angiography and CT angiography of the head and neck with provocative maneuvers did not demonstrate vertebral artery narrowing. However, there was narrowing of the left internal jugular vein due to extrinsic compression from the sternocleidomastoid with leftward head rotation in the setting of hypoplasia of the right internal jugular vein. The patient underwent a cervical venogram which confirmed the finding. Manometric evaluation demonstrated a gradient of 29â mmâ Hg across the stenosis with the head turned leftwards compared with 1â mmâ Hg in the neutral position. The patient was treated with myectomies of the left sternocleidomastoid, posterior belly of the digastric, stylohyoid and omohyoid and styloid process removal. Following surgery, the patient reported complete resolution of symptoms. Repeat venography demonstrated resolution of the stenosis and pressure gradient.
Assuntos
Veias Jugulares/diagnóstico por imagem , Mucopolissacaridose II/complicações , Anormalidade Torcional/complicações , Insuficiência Vertebrobasilar/etiologia , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Constrição Patológica , Humanos , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose II/diagnóstico , Anormalidade Torcional/diagnóstico , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnósticoRESUMO
Hunter syndrome is a multisystem genetic disease in which a significant proportion of morbidity and mortality arise from respiratory dysfunction. Notably, tracheal abnormalities in Hunter syndrome can compromise clinical stability, and management is primarily supportive. We describe here the first successful implementation of aorto-tracheopexy in a 19-year-old patient as a surgical strategy to resolve progressive respiratory deterioration.
Assuntos
Aorta Torácica/cirurgia , Mucopolissacaridose II/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Esternotomia/métodos , Traqueia/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Broncoscopia , Humanos , Masculino , Mucopolissacaridose II/diagnóstico , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to describe the spectral domain optical coherence tomography (SD-OCT) characteristics of patients with retinal manifestations of mucopolysaccharidoses (MPSs) I, II, and IV A. DESIGN: The research was a prospective, observational study. METHODS: Fourteen consecutive patients with variants of MPS and 15 healthy subjects underwent ophthalmic assessments including fundus examinations and SD-OCT. RESULTS: The fundus examinations revealed that four patients (two MPS I and two MPS II) had pigmented retinopathy in both eyes. In addition, one MPS II patient had cystoid macular edema and two MPS II patients had abnormal disc morphology. SD-OCT revealed thinning of the parafoveal photoreceptor inner segment/outer segment (IS/OS; two MPS I and one MPS II) and perifoveal photoreceptor IS/OS (two MPS I and five MPS II). All MPS I and II patients exhibited thickening of the central foveal external limiting membrane (ELM). Fundus and SD-OCT findings were normal in MPS IV A and healthy subjects. The foveal ELM was significantly thicker in MPS I and II patients than in healthy subjects (P =0 .000 and P =0 .000, respectively). The foveal IS/OS was significantly thinner in MPS I, II, and IV A patients than in healthy subjects (P = 0.000, P = 0.000, and P = 0.030, respectively). The foveal retinal pigment epithelium layer was also thinner in MPS II patients than in healthy subjects (P = 0.007) CONCLUSIONS: In MPS, accumulation of glycosaminoglycans in retinal tissue induced retinal degeneration and pigmentary retinopathy. SD-OCT was a useful tool for detecting retinal pathology, particularly changes in ELM and IS/OS.
Assuntos
Mucopolissacaridose II/diagnóstico , Mucopolissacaridose IV/diagnóstico , Mucopolissacaridose I/diagnóstico , Retinose Pigmentar/diagnóstico , Tomografia de Coerência Óptica , Adolescente , Criança , Eletrorretinografia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Mucopolissacaridose I/fisiopatologia , Mucopolissacaridose II/fisiopatologia , Mucopolissacaridose IV/fisiopatologia , Estudos Prospectivos , Retina/fisiopatologia , Retinose Pigmentar/fisiopatologia , Testes de Campo Visual , Campos Visuais/fisiologia , Adulto JovemRESUMO
The aim of this study was to assess the activities of daily living (ADL) in patients with Hunter syndrome (mucopolysaccharidosis II; MPS II) using a newly designed ADL questionnaire. We applied the questionnaire to evaluate clinical phenotypes and therapeutic efficacies of enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). We also explored early signs and symptoms to make early diagnosis feasible. We devised a new ADL questionnaire with three domains: "movement," "movement with cognition," and "cognition." Each domain has four subcategories rated on a 5-point scale based on level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was first administered to 138 healthy Japanese controls (0.33-50 years), and successively, to 74 Japanese patients with Hunter syndrome (4-49 years). The patient cohort consisted of 51 severe and 23 attenuated phenotypes; 20 patients treated with HSCT, 23 patients treated early with ERT (≤8 years), 25 patients treated late with ERT (>8 years), and 4 untreated patients. Among 18 severe phenotypic patients treated by HSCT, 10 were designated as early HSCT (≤5years), while 8 were designated as late HSCT (>5years). Scores from patients with severe phenotypes were lower than controls and attenuated phenotypes in all categories. Among patients with severe phenotypes, there was a trend that HSCT provides a higher ADL score than early ERT, and there was a significant difference in ADL scores between late ERT and HSCT groups. Early ERT and early HSCT provided a higher score than late ERT and late HSCT, respectively. In conclusion, we have evaluated the feasibility of a new questionnaire in control population and patients with Hunter syndrome, leading to a novel evaluation method for clinical phenotypes and therapeutic efficacy. Early treatment with HSCT provides a better consequence in ADL of patients.
Assuntos
Atividades Cotidianas , Terapia de Reposição de Enzimas , Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridose II/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Cognição , Terapia de Reposição de Enzimas/normas , Feminino , Humanos , Iduronidase/uso terapêutico , Lactente , Japão , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose II/diagnóstico , Fenótipo , Inquéritos e Questionários , Adulto JovemRESUMO
Hunter syndrome is caused by deficiency of the lysososmal enzyme iduronate-2-sulphatase that cleaves O-linked sulphate moieties from dermatan sulphate and heparan sulphate and leads to accumulation of GAGs. The disease is a X-linked condition affecting males and rarely females, clinically divided into severe (2/3) and attenuated types. Children with severe form, diagnosed at 12-36 months, have coarse facial feature, short stature, joint stiffness, short neck, broad chest, large head circumference, watery diarrhea, skeletal changes, progressive and profound mental retardation, retinal degeneration' hearing loss, cardiomyopathy, valvular involvement, with progressive thickening and stiffening of the valve leaflets leading to mitral and aortic regurgitation and stenosis . Recurrent and prolonged rhinitis with persistent nasal discharge are the first symptoms of airway disease that manifests itself as noisy breathing and later sleep apnea. Some patients develop ivory-colored skin lesions on the upper back and sides of the upper arms, pathogenomic of Hunter syndrome. The scalp hair becomes coarse, straight and bristly. Inguinal and umbilical hernias occur caused by the disturbed structure of connective tissue and increased liver and spleen volume. Patients with attenuated form have normal intelligence and a milder phenotype. Physical features diagnosed later are similar but less pronounced but progress to severe disease. Sceening is by quantitative assessment of urinary GAGs excretion. Qualitative assessment of GAG by electrophoresis can distinguish the type of mucopolysaccharidosis. Definitive diagnosis is based on enzyme activity assay in leukocytes, fibroblasts or plasma. Molecular testing is recommended mainly for genetic counseling and carrier detection. Limited experience of Haematopoietic stem cell therapy in MPS II showed progressive neurodegeneration. Recombinant 125 Idursulfase, is indicated for long-term treatment. The response appears to depend on the severity of the disease and the age treatment is started, Improvements in a composite endpoint comprising: change in walking distance percentage of predicted forced vital capacity (%FVC) ,decrease in liver and spleen volume and urinary GAG levels were encouraging. Current research is focused on pharmacological chaperones, gene therapy and substrate reduction therapy and therapies that, unlike Idursulfase, do cross the blood-brain barrier.
Assuntos
Terapia de Reposição de Enzimas , Transplante de Células-Tronco Hematopoéticas , Iduronato Sulfatase/uso terapêutico , Mucopolissacaridose II/diagnóstico , Humanos , Mucopolissacaridose II/tratamento farmacológico , Mucopolissacaridose II/cirurgia , PrognósticoRESUMO
INTRODUCCIÓN: La mucopolisacaridosis tipo II y tipo IVA son enfermedades causadas por la deficiencia de las enzimas iduronato 2 sulfato sulfatasa y galactosamina 6 sulfato sulfatasa respectivamente. El depósito resultante de glucosaminoglicanos produce manifestaciones clínicas variadas. Aunque se han propuesto varias alternativas diagnósticas, tales como el examen físico, la cuantificación de glucosaminoglicanos en orina y la cuantificación de la actividad enzimática en leucocitos, la utilidad diagnóstica de esta última no ha sido estudiada en la práctica clínica rutinaria. La posibilidad de ofrecer terapia de reemplazo enzimático a estos pacientes obliga a evaluar la utilidad de la cuantificación de actividad enzimática para confirmar el diagnóstico de estas entidades. OBJETIVO: Evaluar la utilidad diagnóstica de la cuantificación de actividad enzimática de la iduronato 2 sulfato sulfatasa en leucocitos para la confirmación diagnóstica de la MPS tipo II y la galactosamina 6 sulfato sulfatasa en leucocitos para la confirmación diagnóstica de la MPS tipo IVA. Esta revisión no contempla la evaluación de la utilidad diagnóstica del examen físico, glucosaminoglicanos en orina o pruebas moleculares. METODOLOGÍA: Se realizó una búsqueda de las revisiones panorámicas y sistemáticas de los últimos cinco años y estudios de validez diagnóstica, cohortes descriptivas y series de casos sin límite de fecha en MEDLINE, EMBASE, Cochrane, DARE, LILACS y Google. Los artículos debían estar en texto completo, en inglés o español. Se excluyeron artículos que describieran mutaciones o manifestaciones clínicas de un sistema u órgano específico. Los estudios con criterios de elegibilidad fueron evaluados por dos revisores independientes. A los estudios incluidos se extrajo información sociodemográfica, clínica y métodos diagnósticos empleados. RESULTADOS: No se encontró ninguna revisión panorámica, sistemática o estudio de validez diagnóstica para MPS tipo II o IVA. Se incluyeron 3 estudios de serie de casos para MPS tipo II y 13 series de casos para MPS tipo IVA. El 100% de los estudios de MPS tipo II incluyeron la cuantificación enzimática como prueba confirmatoria. El 63.6% (7/11) de las series de casos de MPS tipo IVA incluyeron la cuantificación enzimática en leucocitos como prueba confirmatoria, el 18.1% (2/11) no la incluyeron por falta de disponibilidad de la tecnología y el otro 18.1% (2/11) por publicación del artículo antes de la fecha de introducción de la tecnología. CONCLUSIONES: La cuantificación de la actividad enzimática de la iduronato 2 sulfato sulfatasa y la galactosamina 6 sulfato sulfatasa en leucocitos representa una tecnología diagnóstica útil para confirmar MPS tipo II y MPS tipo IVA respectivamente en pacientes con sospecha clínica de dichas entidades.(AU)
Assuntos
Humanos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose IV/diagnóstico , Leucócitos/enzimologia , Análise Custo-Benefício/economia , ColômbiaRESUMO
BACKGROUND: Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (<12 years). METHODS: In this study, we evaluated: urinary GAG content, hepato/splenomegaly, heart valvulopathies, otorinolaryngological symptoms, joint range of motion, growth, distance covered in the 6-minute walk test, neurological involvement. For data analysis, the 27 patients were divided into three groups according to the age at start of ERT: ≤5 years, >5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a "severe" phenotype were compared with "attenuated" ones. RESULTS: Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. CONCLUSIONS: Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons.
Assuntos
Terapia de Reposição de Enzimas/métodos , Iduronato Sulfatase/uso terapêutico , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Glicosaminoglicanos/urina , Humanos , Lactente , Masculino , Mucopolissacaridose II/urina , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To analyze the mutations of IDS gene in a mucopolysaccharidosis type II (MPSII) family and to make prenatal diagnosis on the high-risk fetus which has been pregnant for eleven weeks. METHODS: IDS gene was analyzed by bidirectional DNA sequencing in 2 patients and their mother, and 5 unaffected individuals. Prenatal diagnosis for the high-risk fetus was performed by chorionic villus sampling after the genotypes was identified. RESULTS: The mutation c.344delA (N115fsX15) was detected in the two patients, and the mother of patients carried the heterozygous c.344delA (N115fsX15) mutation. None of the mutant was detected in the 5 unaffected subjects. The fetus carried c.344delA (N115fsX15) heterozygous mutation and was a carrier. CONCLUSION: The deletion mutation c.344delA (N115fsX15) is causative to the pedigree of MPSII, and prenatal diagnosis is the efficient method to avoid defect birth.
Assuntos
Análise Mutacional de DNA , Glicoproteínas/genética , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/genética , Diagnóstico Pré-Natal , Sequência de Bases , Pré-Escolar , Amostra da Vilosidade Coriônica , Feminino , Doenças Fetais , Predisposição Genética para Doença , Genótipo , Glicoproteínas/metabolismo , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Reação em Cadeia da Polimerase , Gravidez , Análise de Sequência de DNARESUMO
Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders.
Assuntos
Doenças por Armazenamento dos Lisossomos/diagnóstico , Diagnóstico Diferencial , Glucuronidase/metabolismo , Humanos , Liases/metabolismo , Doenças por Armazenamento dos Lisossomos/enzimologia , Erros Inatos do Metabolismo/diagnóstico , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose III/diagnóstico , Mucopolissacaridose IV/diagnóstico , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VII/diagnósticoRESUMO
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by the deficiency of hydrolases involved in the degradative pathway of glycosaminoglycans. In MPS, upper airway obstruction may result from multiple causative factors which may impact severely upon morbidity and mortality. METHODS: We evaluated upper airway obstructive disease and related clinical findings through home sleep study in 19 patients (11 with MPS VI, 4 with MPS I, 4 with MPS II) with MPS followed at Gazi University Pediatric Metabolic Unit. Patients underwent home-based sleep measurements, and sleep respiratory problems were asked in a detailed clinical history. Measurements of apnea, apnea-hypopnea index (AHI), hypopnea index, oxygen desaturation index, and minimal oxygen saturation were obtained through home sleep study. RESULTS: For 19 children, the disorder was normal in 1, mild (AHI=1.5-5/h) in 5, moderate (AHI=5-10/h) in 2, and severe (AHI>10/h) in 11. The prevalence of OSA was 94.7 % (18/19) in patients with MPS. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. Echocardiograms showed evidence of pulmonary hypertension in 13 patients. CONCLUSION: Home sleep study is a quick and accessible screening test to determine the abnormalities of breathing during sleep and enables clinicians to take necessary action for patients with severe manifestations.
Assuntos
Serviços de Assistência Domiciliar , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/epidemiologia , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose I/epidemiologia , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/epidemiologia , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Programas de Rastreamento , Polissonografia/instrumentação , TurquiaRESUMO
Introduction: Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal disorder caused by deficiency of iduronate-2-sulfatase (IDS). In this study, we proposed a new protocol for prenatal diagnosis, using DNA obtained from amniotic fluid cells that did not attach to the bottom of the culture flask after the first medium change. Methods: Four pregnant MPS II carriers were referred to the Medical Genetics Service of Hospital de Clinicas de Porto Alegre for a prenatal diagnosis and identification of the disease, which were performed by polymerase chain reaction (PCR) amplification, restriction fragment length polymorphism, and sequencing according to the mutation previously found in the family. Results: The analysis indicated the absence of mutation in three fetal materials and the presence of mutation in one case. Concomitantly, cytogenetic and biochemical analyses were performed after 12 days of cell culture, and only one case showed absence of enzyme activity, confirming the molecular analysis. Conclusions: This diagnostic protocol designed to provide more robust results and safer genetic counseling suggests that DNA obtained from floating amniotic fluid cells can be used as a source of fetal material to allow a faster alternative for prenatal care through molecular analysis. Determination of IDS gene mutation in fetal amniotic fluid cells together with IDS enzyme activity testing is a rapid, sensitive and accurate method for prenatal diagnosis of MPS II for high-risk pregnant women.