Families\u27 healthcare experiences for children with inherited metabolic diseases: Protocol for a mixed methods cohort study

Introduction Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada. Methods and analysis A two-stage explanatory sequential mixed methods design will be used. Stage 1: quantitative data on healthcare networks and encounter experiences will be collected from 100 parent/guardians through a care map, 2 baseline questionnaires and 17 weekly diaries over 5-7 months. Care networks will be analysed using social network analysis. Relationships between demographic or clinical variables and ratings of healthcare experiences across a range of family centred care dimensions will be analysed using generalised linear regression. Other quantitative data related to family experiences and healthcare experiences will be summarised descriptively. Ongoing analysis of quantitative data and purposive, maximum variation sampling will inform sample selection for stage 2: a subset of stage 1 participants will participate in one-on-one videoconference interviews to elaborate on the quantitative data regarding care networks and healthcare experiences. Interview data will be analysed thematically. Qualitative and quantitative data will be merged during analysis to arrive at an enhanced understanding of care experiences. Quantitative and qualitative data will be combined and presented narratively using a weaving approach (jointly on a theme-by-theme basis) and visually in a side-by-side joint display. Ethics and dissemination The study protocol and procedures were approved by the Children\u27s Hospital of Eastern Ontario\u27s Research Ethics Board, the University of Ottawa Research Ethics Board and the research ethics boards of each participating study centre. Findings will be published in peer-reviewed journals and presented at scientific conferences

Experiences of caregivers of children with inherited metabolic diseases: a qualitative study

Background: We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interactions with the health care system. Methods: From four Canadian centres, we conducted semi-structured telephone interviews with parents/caregivers of children with an IMD who were born between 2006 and 2015 and who were participating in a larger cohort study. Participants were selected with the aim of achieving a diverse sample with respect to treatment centre, IMD, and age of the child. Interviews emphasized the impacts of the disease and its treatment on the child and family and explicitly queried perceptions of interactions with the health care system. We identified emergent themes from the interview data. Results: We completed interviews with 21 parents/caregivers. The 21 children were aged \u3c1 to 7 years old with IMD that included amino acid disorders, urea cycle disorders, fatty acid oxidation disorders, and organic acid disorders or \u27other\u27 IMD. Most parents reported that they and their families had adapted well to their child\u27s diagnosis. Parents used proactive coping strategies to integrate complex disease management protocols into routine family life. An important source of stress was concern about the social challenges faced by their children. Participants reported positive interactions with their most involved health care providers within the metabolic clinic. However, they reported challenges associated with the health care system outside of disease-specific metabolic care, when encountering systems and providers unfamiliar with the child\u27s disease. Conclusions: The successful use of proactive coping strategies among parents of children with IMD in this study suggests the potential value of promoting positive coping and is an important direction for future study. Parents\u27 social concerns for their children were important stressors that warrant consideration by health care providers positioned to support families. Our results with respect to experiences with care highlight the important role of specialized metabolic clinics and point to a need for better coordination of the care that takes place outside the disease-specific management of IMD

Family Experiences with Care for Children with Inherited Metabolic Diseases in Canada: A Cross-Sectional Survey

Background and Objective: Children with inherited metabolic diseases often require complex and highly specialized care. Patient and family-centered care can improve health outcomes that are important to families. This study aimed to examine experiences of family caregivers (parents/guardians) of children diagnosed with inherited metabolic diseases with healthcare to inform strategies to improve those experiences. Methods: A cross-sectional mailed survey was conducted of family caregivers recruited from an ongoing cohort study. Participants rated their healthcare experiences during their child’s visits to five types of healthcare settings common for inherited metabolic diseases: the metabolic clinic, the emergency department, hospital inpatient units, the blood laboratory, and the pharmacy. Participants provided narrative descriptions of any memorable negative or positive experiences. Results: There were 248 respondents (response rate 49%). Caregivers were generally very or somewhat satisfied with the care provided at each care setting. Appropriate treatment, provider knowledge, provider communication, and care coordination were deemed essential aspects of satisfaction with care by the majority of participants across many settings. Memorable negative experiences were reported by 8–22% of participants, varying by setting. Among participants who reported memorable negative experiences, contributing factors included providers’ demeanor, lack of communication, lack of involvement of the family, and disregard of an emergency protocol letter provided by the family. Conclusions: While caregivers’ satisfaction with care for children with inherited metabolic diseases was high, we identified gaps in family-centered care and factors contributing to negative experiences that are important to consider in the future development of strategies to improve pediatric care for inherited metabolic diseases

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies

Hyperleucinosis during infections in maple syrup urine disease post liver transplantation

Maple syrup urine disease (MSUD) is due to biallelic variants in one of the three genes: BCKDHA, BCKDHB, and DBT. Branched-chain alpha-ketoacid dehydrogenase complex deficiency and elevated leucine, valine, isoleucine and alloisoleucine in body fluids are the results. We report hyperleucinosis during intercurrent illnesses in six patients with MSUD post liver transplantation. Patient charts were retrospectively reviewed. Data was entered into an Excel Database. Literature was reviewed. Six patients with MSUD were included who had post liver transplantation hyperleucinosis during an intercurrent illness. Five had encephalopathy. One received hemodialysis for the management of hyperleucinosis. All patients had unrestricted diet. Additionally, there were five patients (one patient included into the current study) reported in the literature. We suggested management considerations for the follow-up of patients with MSUD post liver transplantation after the first episode of unexplained encephalopathy or signs of acute hyperleucinosis during intercurrent illness due to our clinical experience: 1) Healthy: Unrestricted diet and monitoring of leucine levels; 2) Illness: a) home illness management: increased carbohydrate intake b) illness management at hospital: intravenous dextrose, intravenous lipid and daily plasma amino acid monitoring. We report hyperleucinosis and/or encephalopathy as a rare event post liver transplantation in MSUD as a multicenter case series. Hyperleucinosis and/or encephalopathy may occur in both related and unrelated donor liver transplantation. Based on the long-term follow-up of those patients, these suggested management considerations may be revised as per the patients\u27 needs

Clinical and biochemical phenotypes, genotypes, and long-term outcomes of individuals with galactosemia type I from a single metabolic genetics center in Alberta

Background: Galactosemia type I is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase deficiency, encoded by GALT. To investigate the phenotypes, genotypes and long-term outcomes of galactosemia, we performed a retrospective cohort study in our center. Methods: All individuals with galactosemia type I were included. We divided individuals into two groups to compare the outcomes of those treated symptomatically (SymX) and asymptomatically (AsymX). We reviewed electronic patient charts for clinical features, biochemical investigations, molecular genetic investigations, treatments, and outcomes. Results: There were 25 individuals including classic (n = 17), clinical variant (n = 4), and biochemical variant (Duarte) galactosemia (n = 4). Twelve individuals were diagnosed symptomatically (SymX), and 9 individuals were diagnosed asymptomatically (AsymX). We did not include individuals with biochemical variant (Duarte) galactosemia into any of these groups. At the time of the diagnosis, conjugated hyperbilirubinemia was present in 83.3% of SymX group, whereas only 22% of AsymX group. SymX group had hepatomegaly (25%), failure to thrive (33.3%), cataract (16.7%) and sepsis (25%), whereas none of the individuals in the AsymX group had these clinical features. Fourteen variants in GALT were identified including pathogenic/likely pathogenic (n = 12), and likely benign/benign (n = 2) variants. The vast majority of individuals with classic and clinical variant galactosemia were treated with a galactose-lactose-free diet for life (n = 20/21). Intellectual disability was present in 54.5% of the SymX group, and in 37.5% of the AsymX group as a long-term outcome. Tremors were present 50% of the SymX group, and in 22% of the AsymX group as a long-term outcome. Although, intellectual disability and tremors seem to be less common in the AsymX group, there was no statistically significant difference between both groups. Primary ovarian insufficiency was present 50% of the SymX group, whereas in 20% of the AsymX group in post-pubertal females. We report a novel hypomorphic GALT variant (p.Ala303Ser) in one individual with clinical variant galactosemia. We also report an individual with clinical variant galactosemia with normal urine galactitol levels on a normal diet. Conclusion: It seems that newborn screening and early administration of a galactose-lactose-free diet decreases the long-term galactosemia-associated complications but does not prevent them completely. It may be that not all individuals with clinical variant galactosemia may need a galactose-lactose-free diet. It is timely to find new therapeutic strategies that can reduce the frequency of late-onset complications in galactosemia

Additional file 1 of Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic

Additional file 1. Table S1: Newborn screening results are summarized in Table S1. Table S2. All variants and their ACMG classification are summarized in Table S2. Table S3: Biochemical features, illness management, and number of lifetime hospital admissions are summarized in Table S3

Provider perspectives on barriers to and facilitators of family-centred health care delivery for children with inherited metabolic diseases: protocol for a qualitative study

Background: Families have identified challenges related to receiving family-centred health care for children with inherited metabolic diseases (IMDs). We are conducting a multi-phase research program aiming to develop complex interventions to improve care for these children and their families. Towards that aim, we conducted a study (Phase I) to identify and describe family experiences of health care for children with IMDs. Building on that study, in this study (Phase II), we aim to identify the strengths and challenges to providing family-centred health care for children with IMDs and describe the types of strategies that may be helpful to improving such care, from the perspectives of health care personnel. Methods: We will conduct one semi-structured, videoconference or telephone (participant choice) interview with 15 to 30 purposively or snowball sampled participants. Participants will be health care personnel, working in health care institutions or clinical settings anywhere in Canada, who are or have been involved in the care, or administration or decision-making related to care, of one or more children with IMDs. Participants will be asked about their experiences, strengths and challenges related to, and potential strategies to improve, one or more of three topics of interest related to family-centred care: care coordination; family-provider communication; and approaches to care for an unknown condition. We will use framework analysis to analyze the data. Discussion: In the next phase of our research program, we will bring together families of children with IMD, clinicians, decision-makers and methodologists to use the findings from this study, in tandem with our Phase I findings, to develop meaningful interventions that will aim to improve family-centred care for children with IMD and their families