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LGBTQ+ individuals experience health care disparities and difficulty accessing affirming care. Little is known regarding the health and experiences among subpopulations of specific sexual orientations and gender identities (SOGI). We implemented the first LGBTQ + health needs assessment survey in Nassau and Suffolk Counties, New York, to assess individuals' health care experiences, behaviors, access to care, and health care needs. The sample (N = 1150) consisted of many SOGI subgroups. Greater than 60% of respondents reported symptoms of chronic depression; over one third reported disrespectful health care experiences; and two thirds experienced verbal harassment. Bisexual/bicurious, pansexual, queer, gender nonconforming and transgender individuals experienced highest rates of mental health concerns and difficulty accessing care. Behavioral health concerns were also high among Black, multiracial, Hispanic, Asian, young adult, and lower-income respondents. Gaining an understanding of unique differences among LGBTQ+ subgroups can guide implementation of services targeting specific subpopulations to improve access to care and reduce disparities.
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Conducta Sexual , Minorías Sexuales y de Género , Adulto Joven , Humanos , New York , Evaluación de Necesidades , Conducta Sexual/psicología , Identidad de GéneroRESUMEN
Disclaimer:This diagnostic guideline is intended as an educational resource and represents the opinions of the authors, and is not representative of recommendations or policy of the American College of Medical Genetics and Genomics (ACMG). The information should be considered a consensus based on expert opinion, as more comprehensive levels of evidence were not available in the literature in all cases. BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and often fatal lysosomal storage disease. The underlying metabolic defect is deficiency of the enzyme acid sphingomyelinase that results in progressive accumulation of sphingomyelin in target tissues. ASMD manifests as a spectrum of severity ranging from rapidly progressive severe neurovisceral disease that is uniformly fatal to more slowly progressive chronic neurovisceral and chronic visceral forms. Disease management is aimed at symptom control and regular assessments for multisystem involvement. PURPOSE AND METHODS: An international panel of experts in the clinical and laboratory evaluation, diagnosis, treatment/management, and genetic aspects of ASMD convened to review the evidence base and share personal experience in order to develop a guideline for diagnosis of the various ASMD phenotypes. CONCLUSIONS: Although care of ASMD patients is typically provided by metabolic disease specialists, the guideline is directed at a wide range of providers because it is important for primary care providers (e.g., pediatricians and internists) and specialists (e.g., pulmonologists, hepatologists, and hematologists) to be able to identify ASMD.Genet Med advance online publication 13 April 2017.
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Consenso , Enfermedad de Niemann-Pick Tipo A/diagnóstico , Enfermedad de Niemann-Pick Tipo B/diagnóstico , Guías de Práctica Clínica como Asunto , Algoritmos , Biomarcadores , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Pruebas Genéticas/métodos , Humanos , Mutación , Enfermedad de Niemann-Pick Tipo A/etiología , Enfermedad de Niemann-Pick Tipo A/metabolismo , Enfermedad de Niemann-Pick Tipo B/etiología , Enfermedad de Niemann-Pick Tipo B/metabolismo , Fenotipo , Esfingomielina Fosfodiesterasa/genéticaRESUMEN
PURPOSE: Enzyme replacement therapy with olipudase alfa (recombinant human acid sphingomyelinase) is being developed for Niemann-Pick disease type B (NPD B). METHODS: A single-center, open-label, nonrandomized, single-ascending-dose trial evaluated the safety of intravenous olipudase alfa (0.03-1.0 mg/kg) in 11 adults with NPD B. Patients were monitored in the hospital for 72 h after infusion and had follow-up visits on days 14 and 28. RESULTS: Plasma ceramide, a product of sphingomyelin catabolism by olipudase alfa, showed dose-dependent elevations by 6 h postdose, or postinfusion. No serious adverse drug reactions (ADRs) occurred during the study. Acute phase reaction-type ADRs, as evidenced by elevated inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin-8, and calcitonin) and constitutional symptoms (fever, pain, nausea, and/or vomiting) emerged 12-24 h following doses ≥0.3 mg/kg olipudase alfa. Three patients experienced hyperbilirubinemia. The study was terminated after a patient dosed at 1 mg/kg exhibited severe hyperbilirubinemia; he was subsequently diagnosed with Gilbert syndrome. CONCLUSION: The maximum tolerated dose of olipudase alfa in adults with NPD B was 0.6 mg/kg. First-dose ADRs were likely induced by elevated concentrations of ceramide (or its downstream derivatives) generated by the catabolism of accumulated sphingomyelin. Within-patient dose escalation to slowly catabolize sphingomyelin stores may be a strategy to mitigate first-dose ADRs in patients with NPD B.Genet Med 18 1, 34-40.
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Enfermedad de Niemann-Pick Tipo A/tratamiento farmacológico , Enfermedad de Niemann-Pick Tipo B/tratamiento farmacológico , Proteínas Recombinantes/efectos adversos , Esfingomielina Fosfodiesterasa/efectos adversos , Adulto , Proteína C-Reactiva/metabolismo , Relación Dosis-Respuesta a Droga , Terapia de Reemplazo Enzimático/efectos adversos , Terapia de Reemplazo Enzimático/métodos , Femenino , Humanos , Hiperbilirrubinemia , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad de Niemann-Pick Tipo A/enzimología , Enfermedad de Niemann-Pick Tipo B/enzimología , Proteínas Recombinantes/administración & dosificación , Esfingomielina Fosfodiesterasa/administración & dosificación , Esfingomielina Fosfodiesterasa/deficienciaRESUMEN
Niemann-Pick disease type B (NPD-B) is caused by a partial deficiency of acid sphingomyelinase activity and results in the accumulation of lysosomal sphingomyelin (SPM) predominantly in macrophages. Notably, SPM is not significantly elevated in the plasma, whole blood, or urine of NPD-B patients. Here, we show that the de-acylated form of sphingomyelin, lyso-SPM, is elevated approximately 5-fold in dried blood spots (DBS) from NPD-B patients and has no overlap with normal controls, making it a potentially useful biomarker.
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Células Sanguíneas/química , Enfermedad de Niemann-Pick Tipo B/sangre , Fosforilcolina/análogos & derivados , Esfingomielina Fosfodiesterasa/deficiencia , Esfingosina/análogos & derivados , Estudios de Casos y Controles , Pruebas con Sangre Seca , Humanos , Lisosomas/metabolismo , Lisosomas/patología , Macrófagos/metabolismo , Macrófagos/patología , Enfermedad de Niemann-Pick Tipo B/diagnóstico , Enfermedad de Niemann-Pick Tipo B/patología , Fosforilcolina/aislamiento & purificación , Esfingosina/aislamiento & purificaciónRESUMEN
PURPOSE: The purpose of this study was to perform a systematic evaluation of morbidity and mortality in type B Niemann-Pick disease. METHODS: A total of 103 patients with Niemann-Pick disease (49 males, 54 females, age range: 1-72 years) participated in natural history studies through Mount Sinai's International Center for Types A and B Niemann-Pick Disease between 1992 and 2012. RESULTS: Serious morbidities included significant neurological, hepatic, and cardiac disease. Thirteen patients had some degree of neurological impairment. Nine patients had cirrhosis or liver failure requiring transplantation. Coronary artery and valvular heart disease were present in nine patients. Of note, only four patients were oxygen dependent, although progressive pulmonary disease is a well-described feature of Niemann-Pick disease. During the follow-up period, 18 deaths occurred. The median age of death was 15.5 years (range 1-72). Causes of death included pneumonia, liver failure, and hemorrhage. The majority of deaths (12 of 18) occurred in patients <21 years, yielding a mortality rate of 19% in the pediatric population. CONCLUSION: This study demonstrates that Niemann-Pick disease is a life-threatening disorder with significant morbidity and mortality, especially in the pediatric population. The information collected in this series highlights the need for safe, effective therapy for Niemann-Pick disease.
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Enfermedad de Niemann-Pick Tipo B/complicaciones , Enfermedad de Niemann-Pick Tipo B/mortalidad , Esfingomielina Fosfodiesterasa/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Femenino , Hemorragia/etiología , Hemorragia/mortalidad , Humanos , Lactante , Fallo Hepático/etiología , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Morbilidad , Enfermedad de Niemann-Pick Tipo B/epidemiología , Neumonía/etiología , Neumonía/mortalidad , Adulto JovenRESUMEN
INTRODUCTION: Niemann-Pick disease (NPD) due to acid sphingomyelinase deficiency is a lipid storage disease resulting from the accumulation of sphingomyelin, predominantly within cells of the monocyte-macrophage system. In contrast to other lysosomal storage disorders, skeletal involvement in NPD has not been systematically studied. METHODS: Pediatric and adult NPD-B patients underwent medical histories and physical examinations, DEXA scans to measure bone mineral content (BMC), and bone mineral density (BMD) and computed tomography scan or MRI of the abdomen for spleen volume. Z and/or T scores were calculated for the DEXA results. For the pediatric patients adjusted mean BMC (g) and BMD (g/cm(2)) of the lumbar spine, hip, and femoral neck was compared to control subjects. For determination of the relationship between spleen volume and lumbar spine BMD Z score, linear correlation analyses were performed. RESULTS: Lumbar spine Z scores for pediatric patients ranged from 0.061 to -4.879. Statistically significant decreases were observed for the adjusted mean BMC and BMD at the lumbar spine, hip, and femoral neck between the pediatric NPD-B cohort and control subjects. Most NPD-B adults were osteopenic or osteoporotic at one or more sites according the WHO classification of BMD. In NPD-B patients, the degree of splenomegaly was inversely correlated with lumbar spine BMD Z scores. CONCLUSION: Skeletal involvement is a common and previously unrecognized manifestation of NPD-B. The association between splenomegaly and BMD lends further support to spleen size as an indicator of disease severity.
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Cuello Femoral/patología , Vértebras Lumbares/patología , Enfermedad de Niemann-Pick Tipo A/patología , Enfermedad de Niemann-Pick Tipo B/patología , Absorciometría de Fotón/métodos , Adolescente , Densidad Ósea/fisiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults. RESULTS: Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DLCO), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DLCO decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood. CONCLUSIONS: This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.
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Enfermedades Pulmonares Intersticiales , Enfermedad de Niemann-Pick Tipo A , Enfermedades de Niemann-Pick , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esfingomielina Fosfodiesterasa , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this article is to illustrate the various imaging manifestations of Niemann-Pick disease type B using various imaging techniques emphasizing cross-sectional imaging. CONCLUSION: Niemann-Pick disease type B is a multisystem disease that affects the pulmonary, cardiovascular, abdominal, and skeletal systems. Cross-sectional imaging is well suited for detecting and assessing the various manifestations of this disease, which can be highly suggestive of the diagnosis when seen in combination.
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Enfermedad de Niemann-Pick Tipo B/diagnóstico , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía Abdominal , Radiografía Torácica , Tomografía Computarizada por Rayos XRESUMEN
The use of molecular genetic tests for heritable conditions is expected to increase in medical settings, where genetic knowledge is often limited. As part of a project to improve the clarity of genetic test result reports to minimize misunderstandings that could compromise patient care, we sought input about format and content from practicing primary care clinicians. In facilitated workgroup discussions, clinicians from pediatric, obstetrics-gynecology, and family practice provided their perspectives about molecular genetic testing with a focus on the laboratory reporting of test results. Common principles for enhancing the readability and comprehension of test result reports were derived from these discussions. These principles address the presentation of patient- and test-specific information, the test result interpretation, and guidance for future steps. Model test result reports for DNA-based cystic fibrosis testing are presented that were developed based on workgroup discussions, previous studies, and professional guidelines. The format of these model test reports, which are applicable to a variety of molecular genetic tests, should be useful for communicating essential information from the laboratory to health care professionals.
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Técnicas de Laboratorio Clínico/normas , Pruebas Genéticas/normas , Registros Médicos/normas , Rol del Médico , HumanosRESUMEN
PURPOSE: To evaluate the extent of complementary and alternative medicine use and perceived effectiveness in patients with lysosomal storage diseases. METHODS: A 26-item survey was distributed to 495 patients with type 1 Gaucher, Fabry, and type B Niemann-Pick diseases who were seen at the Lysosomal Storage Disease Program at the Mount Sinai School of Medicine. Survey responses were entered into an access database and analyzed using descriptive statistics. RESULTS: Surveys were completed by 167 respondents with an overall response rate of 34%. Complementary and alternative medicines were used by 45% of patients with type 1 Gaucher disease, 41% of patients with Fabry disease, and 47% of patients with type B Niemann-Pick for symptoms related to their disease. Complementary and alternative medicines were used most frequently by adult females (55%), in patients who reported having one or more invasive procedures due to their disease, patients who use one or more conventional medical therapies, or those with depression and/or anxiety. Overall perceived effectiveness of complementary and alternative medicine supplements was low; however, complementary and alternative medicine therapies were perceived as effective. CONCLUSION: Complementary and alternative medicines are commonly used among patients with lysosomal storage diseases. Assessment of the effectiveness of these approaches in the lysosomal storage diseases is needed, and physicians should be aware of complementary and alternative medicine therapies used by patients to evaluate safety and possible drug interactions.
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Terapias Complementarias/estadística & datos numéricos , Enfermedades por Almacenamiento Lisosomal/terapia , Adolescente , Adulto , Niño , Femenino , Humanos , Enfermedades por Almacenamiento Lisosomal/epidemiología , Enfermedades por Almacenamiento Lisosomal/psicología , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Percepción/fisiología , Médicos de Familia/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer. Given their substantially elevated risk for breast cancer, BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy. To help BRCA1/2 carriers make this decision, the authors developed a computer-based interactive decision aid that was tested against usual care in a randomized controlled trial. DESIGN: After the completion of genetic counseling, 214 female (aged 21-75) BRCA1/BRCA2 mutation carriers were randomized to Usual Care (UC; N = 114) or Usual Care plus Decision Aid (DA; N = 100) arms. UC participants received no additional intervention. DA participants were sent the CD-ROM DA to view at home. MAIN OUTCOME MEASURES: The authors measured final management decision, decisional conflict, decisional satisfaction, and receipt of risk reducing mastectomy at 1-, 6-, and 12-months postrandomization. RESULTS: Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk. Within this group, the DA led to an increased likelihood of reaching a management decision (OR = 3.09, 95% CI = 1.62, 5.90; p < .001), decreased decisional conflict (B = -.46, z = -3.1, p <002), and increased satisfaction (B = .27, z = 3.1, p = .002) compared to UC. Among carriers who had already made a management decision by the time of randomization, the DA had no benefit relative to UC. CONCLUSION: These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support.
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Neoplasias de la Mama/genética , Toma de Decisiones , Genes BRCA1 , Genes BRCA2 , Pruebas Genéticas/psicología , Satisfacción del Paciente , Adulto , Anciano , Femenino , Asesoramiento Genético , Humanos , Mastectomía , Persona de Mediana Edad , Medición de RiesgoRESUMEN
Previous studies have suggested that patient care may be compromised as a consequence of poor communication between clinicians and laboratory professionals in cases in which molecular genetic test results are reported. To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms. We found instances in which result reports for simulated diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis. Similarly, reports based on simulated scenarios for carrier testing were problematic when no mutations were identified, and the patient's race/ethnicity and family history were not discussed in reference to residual risk of disease. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency. These findings are reviewed in light of what efforts should be taken to improve the quality of test-ordering and result-reporting practices.
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Sistemas de Información en Laboratorio Clínico/normas , Técnicas de Laboratorio Clínico/normas , Fibrosis Quística/genética , Pruebas Genéticas , Garantía de la Calidad de Atención de Salud/normas , Fibrosis Quística/diagnóstico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Análisis Mutacional de ADN , Tamización de Portadores Genéticos/métodos , Servicios Genéticos , Humanos , Mutación , Medición de RiesgoRESUMEN
OBJECTIVE: To compare data on the practices of molecular genetic testing (MGT) in laboratories in the United States with those in 18 other countries. METHODS: A Web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on three continents was carried out, and the response from U.S. laboratories compared to all others. Quality assurance and reporting indices were developed and calculated for each responding laboratory. RESULTS: A comparison of U.S. results with all other countries identified differences in laboratory setting, personnel qualifications, and the specific tests being offered, but similar rates of adherence to MGT quality standards and reporting practices were found. The survey also documented substantial transborder flow of specimens, most commonly due to the lack of availability of the test in the United States or because the test was available only through a research protocol, highlighting the need for common reporting and practice guidelines for the international MGT community. CONCLUSION: The findings presented here provide further support for the need to consider the application of the Organisation for Economic Cooperation and Development (OECD) Guidelines and the establishment of compatible accreditation programs or equivalent mechanisms across national borders to ensure the quality of laboratory services and the clinical usefulness of molecular genetic test reports for referred specimens.
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Pruebas Genéticas , Laboratorios/normas , Técnicas de Diagnóstico Molecular , Acreditación , Asia , Confidencialidad , Recolección de Datos/métodos , Europa (Continente) , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Humanos , Consentimiento Informado , Agencias Internacionales/normas , Internet , Personal de Laboratorio Clínico/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , América del Norte , Control de Calidad , Estados UnidosRESUMEN
OBJECTIVE: Previous studies have identified specific attitudes (pros and cons) about BRCA testing held by women of African descent that are associated with decisions to participate in testing. These testing attitudes may be determined, in part, by temporal orientation, or how one perceives the significance of events and the consequences of their actions in terms of past, present, and future. The current study explored the relationship between temporal orientation and pros and cons of BRCA testing among 140 women of African descent with a family history suggestive of a genetic mutation predisposing to breast cancer. METHODS: Participants completed measures of temporal orientation and genetic testing attitudes. RESULTS: Multivariate analyses indicated that future orientation was positively associated with perceived pros of testing. Additional analyses revealed significant associations between temporal orientation and specific item subsets related to the negative and positive impact of testing on family and personal control over one's health. CONCLUSION: These results support an association between temporal orientation and attitudes about BRCA testing among women of African descent with family histories of breast cancer. PRACTICE IMPLICATIONS: Findings support exploration of temporal orientation in future research on BRCA testing decisions among women of African descent and this construct's importance in developing decision aids and tailoring genetic counseling.
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Negro o Afroamericano/etnología , Neoplasias de la Mama/genética , Pruebas Genéticas , Aceptación de la Atención de Salud/etnología , Percepción del Tiempo , Mujeres/psicología , Adulto , Negro o Afroamericano/educación , Negro o Afroamericano/genética , Anciano , Análisis de Varianza , Neoplasias de la Mama/diagnóstico , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas/métodos , Pruebas Genéticas/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , New York , Orientación , Análisis de Regresión , Factores Socioeconómicos , Encuestas y Cuestionarios , Factores de Tiempo , Mujeres/educaciónRESUMEN
Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and often fatal lysosomal storage disease caused by the deficiency of the enzyme acid sphingomyelinase (ASM) resulting in accumulation of sphingomyelin in target tissues. Little is known regarding predictors of disease-related morbidity, healthcare use, and lifestyle impact in adults with chronic disease. A multinational retrospective study collected data on the burden of illness and healthcare resource use for 100 patients across the clinical spectrum of ASMD, including those with rapidly progressive infantile neurovisceral disease (n = 13) and those with the more slowly progressive chronic neurovisceral (n = 6) and chronic visceral (n = 81) disease. Growth was subnormal throughout childhood for all patients with chronic neurovisceral disease and for 50% of patients with chronic visceral disease. Developmental delay, regression, and/or learning disabilities were reported in 40% of patients with chronic neurovisceral ASMD and 21% of patients with chronic visceral ASMD. Outpatient therapy or home healthcare was required for 50% of patients with chronic neurovisceral disease and 12% of patients with chronic visceral disease. Disease-related disability for patients with chronic disease resulted in need for home schooling for 16% of patients and compromised work ability for 22% of patients. Grade school was the highest level of education for 22% of patients older than 13 years of age.
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OBJECTIVE: To collect data on the practices of molecular genetic testing (MGT) laboratories for the development of national and international policies for quality assurance (QA). METHODS: A web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on 3 continents. QA and reporting indices were developed and calculated for each responding laboratory. RESULTS: Laboratory setting varied among and within countries, as did qualifications of the directors. Respondents in every country indicated that their laboratory receives specimens from outside their national borders (64%, n = 529). Pair-wise comparisons of the QA index revealed a significant association with the director having formal training in molecular genetics (p < 0.005), affiliation with a genetics unit (p = 0.003), accreditation of the laboratory (p < 0.005) and participation in proficiency testing (p < 0.005). Research labs had a lower mean report score compared to all other settings (p < 0.05) as did laboratories accessioning <150 samples per year. CONCLUSION: MGT is provided under widely varying conditions and regulatory frameworks. The data provided here may be a useful guide for policy action at both governmental and professional levels.
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Biología Molecular/métodos , Confidencialidad , Recolección de Datos/métodos , Electrónica , Humanos , Consentimiento Informado , Cooperación Internacional , Personal de Laboratorio Clínico/normas , Biología Molecular/normas , Control de Calidad , Encuestas y CuestionariosRESUMEN
Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration, leading to death typically by the age of 3 years, most often from respiratory failure. In contrast, the clinical phenotype and life expectancy of patients with NPD B may vary widely. Almost all patients have hepatosplenomegaly and an atherogenic lipid profile, and most patients have interstitial lung disease with progressive impairment of pulmonary function and hematologic abnormalities including cytopenias. Other common clinical manifestations include liver dysfunction, heart disease, skeletal abnormalities and growth delays. Some patients with ASMD who survive beyond early childhood have intermediate phenotypes (variant NPD B) characterized by combinations of non-neurologic and mild to severe neurologic symptoms. The physical and psychosocial burden of illness in patients with NPD B is substantial. Common symptoms include shortness of breath, joint or limb pain, abdominal pain, bleeding and bruising. The disease often leads to chronic fatigue, limited physical or social activity and difficulties in performing daily activities or work. Many patients die before or in early adulthood, often from pneumonia/respiratory failure or liver failure. Available treatments are limited to symptom management and supportive care. An enzyme replacement therapy currently in clinical development is expected to be the first treatment addressing the underlying pathology of the disease. Early diagnosis and appropriate management are essential for reducing the risk of complications. While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.
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Enfermedades de Niemann-Pick/patología , Esfingomielina Fosfodiesterasa/metabolismo , Causas de Muerte , Costo de Enfermedad , Humanos , Incidencia , Enfermedades de Niemann-Pick/epidemiología , Enfermedades de Niemann-Pick/genética , Enfermedades Raras , Esfingomielina Fosfodiesterasa/genéticaRESUMEN
The purpose of this study was to determine whether physicians refer women with early onset breast cancer for genetic testing for BRCA1 and BRCA2, and how women respond to being offered testing and use the results. A web-based survey was distributed to 1221 women with early onset breast cancer. The survey included 158 questions divided into the following sections: demographics, family history of cancer, medical history, treatment history, and experience with genetic testing. Of 551 women diagnosed since 1993 who responded to the survey (45.1%), less than half (45%, n = 246) had ever discussed genetic testing with their physician and/or been referred to see a genetic counselor. Women with a family history of cancer (53%) and Ashkenazi Jewish women (81%) were more likely to have been referred. Of those who had discussed testing, 60% had undergone or were interested in testing. Overall 92 women were tested and 19 (20.6%) of these tested positive for a deleterious BRCA1 or BRCA2 mutation. Fourteen (74%) who tested positive subsequently underwent prophylactic surgery. Satisfaction with counseling and the decision to be tested was high. Among women who were not offered testing, the fact that the test had not been offered by their physician (89%), and fear of discrimination (83%) were the two most frequently cited factors for lack of interest in testing. A substantial number of women are not being referred to genetic counseling and/or testing after a diagnosis of early onset breast cancer. Among those who were tested, there was high interest in prophylactic surgery after confirmation of a BRCA1/2 mutation.
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Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético , Mutación , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etnología , Femenino , Asesoramiento Genético/normas , Pruebas Genéticas , Encuestas de Atención de la Salud , Humanos , Persona de Mediana Edad , Educación del Paciente como Asunto , Derivación y ConsultaAsunto(s)
Trasplante de Médula Ósea/ética , Trasplante de Médula Ósea/métodos , Ética Médica , Síndrome de Klinefelter/sangre , Síndrome de Klinefelter/genética , Donantes de Tejidos , Síndrome de Wiskott-Aldrich/terapia , Preescolar , Femenino , Asesoramiento Genético , Antígenos HLA/química , Humanos , Lactante , Masculino , Embarazo , Diagnóstico Prenatal , Trasplante Homólogo/métodos , Síndrome de Wiskott-Aldrich/genéticaRESUMEN
Autism is a heterogeneous group of complex developmental disabilities that result from a number of possible etiologies. There are a well-known number of comorbidities associated with autism spectrum disorders (ASD), including, commonly, gastrointestinal (GI) pathology, which can include variable combinations of constipation, diarrhea, abdominal pain, gastroesophageal reflux, and vomiting. An American Academy of Pediatrics consensus panel has recommended that prospective studies be carried out to determine the prevalence of GI disorders in ASD and their pathophysiologic basis. In a recent article, Williams et al. [B. L. Williams, M. Hornig, T. Parekh, and W. I. Lipkin, mBio 3(1):e00261-11, 2012] have provided one such study of autism with GI comorbidities by presenting evidence of Sutterella species in ileal mucosal biopsy specimens from patients diagnosed with ASD but not in control children with GI symptoms, suggesting a specific role for Sutterella in ASD. Sutterella sequences represented ~1 to 7% of the total bacterial sequences, and this is a very large effect size on the ileal mucosal composition of the autism phenotype, rivaling or perhaps exceeding the effect size of the ileal Crohn's disease phenotype. This study opens a new field of investigation to study the etiology or consequences of GI comorbidities in ASD.