A Qualitative Study: Mothers' Experiences of Their Child's Late-Onset Pompe Disease Diagnosis Following Newborn Screening.
Ontology highlight
ABSTRACT:
SUBMITTER: Crossen K
PROVIDER: S-EPMC9326644 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Late-onset Pompe disease (LOPD) is a rare treatable lysosomal storage disorder characterized by progressive lysosomal glycogen accumulation and muscle weakness, with often a limb-girdle pattern. Despite published guidelines, testing for LOPD is often overlooked or delayed in adults, owing to its low frequency compared to other muscle disorders with similar muscle patterns. Next-generation sequencing has the capability to test concurrently for several muscle disorders. This could potentially lead to increased diagnosis of LOPD, disorders with non-specific muscle weakness or atypical patients.We developed a gene panel to further study its clinical utility in a cohort of patients with suspected muscle disorders. We designed a gene panel to analyze the coding sequences and splice site junctions of GAA causing LOPD, along with 77 other genes causing muscle disorders with overlapping phenotypes.At a median coverage of ~200X (sequences per base), all GAA exons were successfully covered with >20X and only 0.3 % of exons across all genes were <20X. The panel showed an excellent sensitivity (100 %) and specificity (98 %) across all selected genes, using known variations in Pompe patients and controls. We determined its clinical utility by analyzing 34 patients with suspected muscle disorders of undetermined etiology and various muscle patterns, who were referred or followed in neuromuscular and genetics clinics. A putative diagnosis was found in up to 32 % of patients. The gene panel was instrumental in reaching a diagnosis in atypical patients, including one LOPD case. Acid alpha-glucosidase activity was used to confirm the molecular results in all patients.This work highlights the high clinical utility of gene panels in patients with suspected muscle disorders and its potential to facilitate the diagnosis of patients showing non-specific muscle weakness or atypical phenotypes. We propose that gene panels should be used as a first-tier test in patients with suspected muscle disorders of undetermined etiology, which could further increase overall diagnosis of muscle conditions, and potentially reduce diagnostic delay. Further studies are necessary to determine the impact of first-tier gene panels on diagnostic delay and on treatment outcome for LOPD.
| S-EPMC4727295 | biostudies-literature
Project description:There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.
| S-EPMC7556025 | biostudies-literature
Project description:OBJECTIVE: To investigate the prevalence and severity of fatigue in adult patients with Pompe disease. METHODS: The Fatigue Severity Scale (FSS) was assessed in an international population of 225 adults with Pompe disease, a metabolic disorder presenting as a slowly progressive proximal myopathy. The FSS scores were compared to those of healthy controls and the relationship between the level of fatigue and other patient characteristics was investigated. RESULTS: The mean age of the participants was 47 (SD 13) years and the mean disease duration 11 (SD 8) years. 43% used a wheelchair and 46% had respiratory support, 29% needed both. 67% of the participants had a FSS score > or =5, indicating severe fatigue. The mean FSS score was 5.2 (SD 1.5), which was significantly higher than that of healthy controls (p < 0.001). Fatigue was not related to age, sex or disease duration. Patients who used a wheelchair or respiratory support were on average more fatigued than those who did not (p = 0.01). However, of the patients who did not use these aids, 59% also had a FSS score > or =5. FSS scores were highest among patients who reported a high frequency of sleep disorders, but patients who never experienced sleep difficulties were also fatigued (mean FSS score = 4.8). CONCLUSION: Fatigue is highly prevalent among both mildly and severely affected adult patients with Pompe disease. The FSS appears a useful tool in assessing fatigue in Pompe disease.
| S-EPMC2779379 | biostudies-other
Project description:PURPOSE:The urinary glucose tetrasaccharide, Glc?1-6Glc?1-4Glc?1-4Glc (Glc4), is a biomarker of glycogen accumulation and tissue damage and is elevated in patients with Pompe disease. We report baseline urinary Glc4 concentrations for patients with classic infantile-onset or late-onset Pompe disease, and those with a pseudodeficiency of acid alpha-glucosidase (GAA), identified through newborn screening (NBS) in Taiwan. METHODS:Infants identified through NBS with (1) classic infantile-onset Pompe disease (NBS-IOPD) (n?=?7) defined as patients with evidence for hypertrophic cardiomyopathy by EKG, X-ray, and echocardiogram, (2) a late-onset phenotype (NBS-LOPD) (n?=?13) defined as patients without evidence for cardiomyopathy, (3) a GAA pseudodeficiency (n?=?58), and (4) one patient with LOPD diagnosed in infancy due to family history were consented to the study. Four infants diagnosed after the onset of clinical symptoms (CLIN-IOPD) were included for comparison. Glc4 concentrations in dried urine samples on filter paper were determined using tandem mass spectrometry. RESULTS:Baseline Glc4 concentrations were at or above the 90th centile of the age-matched reference range for the NBS-IOPD cohort. The median Glc4 level for this group was lower than that of the CLIN-IOPD group, although not at the level of significance (p?=?0.07), but was significantly higher than that of the NBS-LOPD group (p?<?0.05). Baseline Glc4 was not elevated for the NBS-LOPD and GAA pseudodeficiency cohorts and remained low for late-onset patients that did not require treatment before the age of three years. CONCLUSION:Baseline urinary Glc4 is elevated in neonates with infantile-onset Pompe disease identified through NBS.
| S-EPMC4501239 | biostudies-literature
Project description:BackgroundLate-onset Pompe Disease (LOPD) is a rare, heterogeneous disease manifested by a range of symptoms varying in severity. Research establishing the frequency of these symptoms and their impact on patients' daily lives is limited. The objective of this study was to develop a conceptual model that captures the most relevant symptoms and functional limitations experienced by patients with LOPD, to inform the development of new patient-reported outcome (PRO) tools.MethodsA preliminary conceptual model was constructed following a literature review and revised through interviews with expert clinicians to identify important and relevant concepts regarding symptoms and impacts of LOPD. This preliminary model informed the development of a qualitative patient interview guide, which was used to gather the patient perspective on symptoms and impacts relating to LOPD or its treatment (including symptom/impact frequency and levels of disturbance). Patient interviews aided further refinement of the conceptual model. The findings from the patient interviews were triangulated with the literature review and clinician interviews to identify the most relevant and significant effects of LOPD from the patient perspective.ResultsMuscle weakness, fatigue, pain, and breathing difficulties (especially while lying down) were the most common and highly disturbing symptoms experienced by patients. Limitations associated with mobility (e.g., difficulty rising from a sitting position, getting up after bending) and activities of daily living, (e.g., reduced ability to participate in social/family activities or work/study) were the most frequently reported impacts with the highest levels of disturbance on the patient's daily life. These identified symptoms and impacts were included in the new conceptual model of disease.ConclusionsThis qualitative patient interview study, also informed by a literature review and clinician interviews, identified the most frequent and relevant symptoms and the functional impact of LOPD on patients. The study interviews also captured the patient-preferred language to describe symptoms and impacts of LOPD. The results from this study can be used to develop future PRO instruments that are tailored to the specific symptoms and impacts experienced by patients with LOPD.
| S-EPMC8513325 | biostudies-literature
Project description:Pompe disease is a rare metabolic disorder due to deficiency of the lysosomal acid alpha-glucosidase (GAA) that causes glycogen accumulation in all tissues with a predominant involvement of skeletal muscle. The late onset form of Pompe disease (LOPD) is characterized by a progressive weakness of proximal and axial muscles, often mimicking limb-girdle muscular dystrophies or inflammatory myopathies, with respiratory distress mainly due to a diaphragmatic weakness. Diagnostic delay is still common, and clinicians need a high index of suspicion to recognize this condition because the disorder is quite rare, the clinical spectrum is wide, and signs and symptoms are not distinguishable from those in other neuromuscular disorders that present in a similar fashion. Diagnostic laboratory tests are quite fast and reliable to detect the enzymatic deficiency. Enzyme replacement therapy has been available for several years, and other new therapeutic strategies such as gene therapy are underway. Here, we discuss the main diagnostic tools currently used for the evaluation of patients with suspected LOPD.
| S-EPMC6642940 | biostudies-literature
Project description: Not available
| S-EPMC6494567 | biostudies-literature
Project description:PurposeIn Alberta, the high occurrence of late preterm infants and early hospital discharge of mother-infant dyads has implications for postpartum care in the community. Shortened hospital stay and complexities surrounding the care of biologically and developmentally immature late preterm infants heighten anxiety and fears. Our descriptive phenomenological study explores mothers' experience of caring for their late preterm infants in the community.MethodsEleven mothers were interviewed using a semi-structured interview guide. Interview transcripts were analysed using an interpretive thematic approach.FindingsThe mothers' hospital experience informed their perspective that being a late preterm infant was not a "big deal," and they tended to treat their infant as normal. "Feeding was really problem," especially the variability in feeding effectiveness, which was not anticipated. Failing to recognize late preterm infants' feeding distress exemplified lack of knowledge of feeding cues and tendencies to either rationalize or minimize feeding concerns. Public health nurses represent a source of informational support for managing neonatal morbidities associated with being late preterm; however, maternal experiences with public health nurses varied. Some nurses used a directive style that overwhelmed certain mothers. Seeing multiple public health nurses and care providers was not always effective, given inconsistent and contradictory guidance to care. These new and changing situations increased maternal anxiety and stress and influenced maternal confidence in care. Fathers, family, and friends were important sources of emotional support.ConclusionAfter discharge, mothers report their lack of preparation to meet the special needs of their late preterm infants. Current approaches to community-based care can threaten maternal confidence in care. New models and pathways of care for late preterm infants and their families need to be responsive to the spectrum of feeding issues encountered, limit duplication of services, and ensure consistent and effective care that parents will accept.
| S-EPMC5363959 | biostudies-literature
Project description:BACKGROUND: Developments in enzyme replacement therapy have kindled discussions on adding Pompe disease, characterized by progressive muscle weakness and wasting, to neonatal screening. Pompe disease does not fit traditional screening criteria as it is a broad-spectrum phenotype disorder that may occur in lethal form in early infancy or manifest in less severe forms from infancy to late adulthood. Current screening tests cannot differentiate between these forms. Normally, expanding screening is discussed among experts in advisory bodies. While advisory reports usually mention the procedures and outcome of deliberations, little is known of the importance attached to different arguments and the actual weighing processes involved. In this research we aim to explore the views of a wide range of relevant professionals to gain more insight into the process of weighing pros and cons of neonatal screening for Pompe disease, as an example of the dilemmas involved in screening for broad-spectrum phenotype disorders. METHODS: We conducted 24 semi-structured interviews with medical, lab, insurance and screening professionals, and executive staff of patient organisations. They were asked about their first reaction to neonatal screening for Pompe disease, after which benefits and harms and requirements for screening were explored in more detail. RESULTS: Advantages included health gain by timely intervention, avoiding a diagnostic quest, having a reproductive choice and gaining more knowledge about the natural course and treatment. Being prepared was mentioned as an advantage for the later manifesting cases. Disadvantages included treatment costs and uncertainties about its effect, the timing of treatment in later manifesting cases, the psychological burden for the patient-in-waiting and the family. Also the downsides of having prior knowledge as well as having to consider a reproductive option were mentioned as disadvantages. CONCLUSION: When weighing pros and cons, interviewees attach different importance to different arguments, based on personal and professional views. Professionals expect benefits from neonatal screening for Pompe disease, especially for early-onset cases. Some interviewees valued screening in later manifesting cases as well, while stressing the need for adequate support of pre-symptomatic patients and their families. Others considered the psychological burden and uncertainties regarding treatment as reasons not to screen.
| S-EPMC4139142 | biostudies-literature
Project description:Preeclampsia is a hypertensive disorder of pregnancy that affects approximately 2-5% of all pregnancies, contributes to 4 of the top 10 causes of pregnancy-related deaths, and remains a long-term risk factor for cardiometabolic diseases. Yet, little is still known about the molecular mechanisms that lead to this disease. There is evidence that some cases have a genetic cause. However, it is well appreciated that harmful factors in the environment, such as poor nutrition, stress, and toxins, may lead to epigenetics changes that can contribute to this disease. DNA methylation is one of the epigenetic modifications known to be fairly stable and impact gene expression. Using DNA from buccal swabs from pregnant women, we analyzed global DNA methylation among pregnancies complicated by preeclampsia at <32 weeks (early) and >37 weeks (late) against uncomplicated pregnancies, as well as newborns from these pregnancies. We found significant differentially methylated regions between pregnancies complicated by preeclampsia compared to normal pregnancies adjacent or within genes that are important for placentaton, embryonic development, cell adhesion, inflammation (e.g., the cadherin pathway) and many reported to be expressed in tissues relevant to preeclampsia (i.e. brain, heart, kidney, and placenta). As this study was performed on DNA extracted from cheek swabs, this opens the way to future studies in different tissues, aimed at identifying possible biomarkers of risk and early detection, develop targeted interventions, and reduce the progression of this life-threatening disease.
2023-11-13 | GSE245779 | GEO