Establishing how much improvement in lung function and distance walked is clinically important for adult patients with Pompe disease

Background and purpose: Pompe disease is a rare, inheritable, progressive metabolic myopathy. This study aimed to estimate the minimal clinically important difference (MCID) for an improvement in forced vital capacity in the upright seated position (FVCup) and the 6-min walk test (6MWT) after a year of treatment with enzyme replacement therapy. Methods: Data were obtained from two prospective follow-up studies. Between-group and within-group MCIDs were estimated using anchor-based methods. Additionally, a distribution-based method was used to generate supportive evidence. As anchors, self-reported change in health and in physical functioning, shortness of breath and a categorization of the Short-Form 36 Physical Component Summary score were used. Anchor appropriateness was assessed using Spearman correlations (absolute values ≥0.29) and a sufficient number of observations in each category. Results: In all, 102 patients had at least one FVCup or 6MWT measurement during enzyme replacement therapy. Based on the anchors assessed as appropriate, the between-group MCID for an improvement in FVCup ranged from 2.47% to 4.83% points. For the 6MWT, it ranged from 0.35% to 7.47% points which is equivalent to a distance of 2.18–46.61 m and 1.97–42.13 m for, respectively, a man and a woman of age 50, height 1.75 m and weight 80 kg. The results of the distribution-based method were within these ranges when applied to change in the outcome values.Conclusion: The MCIDs for FVCup and 6MWT derived in this study can be used to interpret differences between and within groups of patients with Pompe disease in clinical trials and cohort studies.</p

Newborn screening for pompe disease? a qualitative study exploring professional views

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

Newborn screening for pompe disease? A qualitative study exploring professional views

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

Health-Related Quality of Life and Fatigue in Children with Pompe Disease

Objective: Pompe disease is an inheritable metabolic myopathy caused by the deficiency of the lysosomal enzyme acid-⍺-glucosidase. The aim of this study was to investigate self-reported and parent-reported health related quality of life (HR-QOL) and fatigue in children with Pompe disease. Study design: In this cross-sectional study, the validated Child Health Questionnaire and PedsQL Multidimensional Fatigue Scale were used to respectively measure (both self-reported and parent-reported) HR-QOL and fatigue in children with Pompe disease. Results: In total, of 24 patients with Pompe disease (and their parents) participated, with a median age of 9.6 years [IQR 7.7-11.9], 14 had classic infantile Pompe disease. Self-reported HR-QOL was comparable with the healthy Dutch population on most domains, and patients with the classic infantile type scored mainly lower on physical functioning. Parents of patients with classic infantile Pompe disease reported a significantly lower HR-QOL of their children on 9 domains and parents of patients with (non-classic) childhood-onset Pompe disease on 5 domains. Self-reported fatigue levels in children with classic infantile Pompe disease were increased for 2 of 3 domains compared with healthy peers, and fatigue in patients with non-classic Pompe disease did not differ. Parents of patients with classic infantile Pompe disease reported greater levels of fatigue in all 3 domains compared with healthy children, whereas parents of children with childhood-onset disease scored greater on the cognitive fatigue domain. Conclusions: Children with Pompe disease report comparable HR-QOL on most domains compared with healthy peers. Contrarily, parent-reported HR-QOL was substantially lower on most domains compared with references values. As expected in relation to disease severity, unfavorable effects on HR-QOL and fatigue were more pronounced in patients with classic infantile Pompe disease.</p

A case of adult Pompe disease presenting with severe fatigue and selective involvement of type 1 muscle fibers

AbstractWe present a case of adult Pompe disease (acid maltase deficiency) with an uncommon clinical presentation characterized by severe fatigue and myalgia prior to the onset of limb girdle weakness. Remarkably, the muscle biopsy demonstrated selective involvement of type 1 muscle fibers. The cause and clinical effects of fiber type specific involvement are currently unknown, but the phenomenon might contribute to the clinical heterogeneity in Pompe disease and the variable response to enzyme replacement therapy

The impact of COVID-19 infection, the pandemic and its associated control measures on patients with Pompe disease

Background: Patients with Pompe disease, a rare metabolic myopathy, were thought to be at increased risk of severe COVID-19 disease during the pandemic. In addition, the lockdown may have affected their regular treatment. Objective: To assess the perceived effect of COVID-19 infection and of the pandemic on the treatment, and physical and mental health of patients with Pompe disease. Methods: Patients with Pompe disease over 16 years of age participated in an international, cross-sectional, online survey (September 20, 2022–November 7, 2022). The questionnaire, available in eight languages, consisted of 89 questions divided into 3 parts: (A) severity of Pompe disease, (B) COVID-19 precautions and infection(s) and (C) effects of the COVID-19 pandemic. Results: Among 342 respondents, originating from 25 different countries, 47.6% experienced one or more COVID-19 infections. While most recovered within 4 weeks (69.7%) and only eight patients needed to be admitted to the hospital, 42.2% of patients experienced an impact of the infection on their overall condition, respiratory status and/or mobility status. More severely affected patients took more stringent control measures. The pandemic additionally caused interruptions in medical care in many patients (56.0%) and 17.2% of patients experienced interruptions of enzyme replacement therapy. The pandemic also affected many patients’ disease severity (27.7%), mental health (55.4%) and feeling of loneliness (43.4%). Conclusion: COVID-19 infection(s) and the pandemic affected the treatment, physical health and mental health of patients with Pompe disease, emphasizing the importance of continued patient centered care during a difficult time such as the COVID-19 pandemic.</p

Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy

Background: Pompe disease is a rare lysosomal storage disorder characterized by muscle weakness and wasting. The majority of adult patients have slowly progressive disease, which gradually impairs mobility and respiratory function and may lead to wheelchair and ventilator dependency. It is as yet unknown to what extent the disease reduces the life span of these patients. Our objective was to determine the survival of adults with P