Assessment of quality of life of the children and parents affected by inborn errors of metabolism with restricted diet: preliminary results of a cross-sectional study (original) (raw)

Health Status of French Young Patients with Inborn Errors of Metabolism with Lifelong Restricted Diet

The Journal of Pediatrics, 2020

Objective To describe the health status of young patients affected by inborn errors of metabolism that require adherence to a restricted diet (IEMRDs) and to describe and compare their self-and proxy (parent)-reported quality of life (QoL) with reference values. Study design A cross-sectional study was conducted in 2015-2017 in patients affected by IEMRDs (except phenylketonuria) younger than 18 years. Data collection was based on medical records, clinical examinations, parents' and children's interviews, and self-reported questionnaires. Measurements included clinical and healthcare data, child and family environment data, and self-and proxy (parent)-reported QoL. Results Of the 633 eligible participants, 578 were recruited (50.3% boys; mean age: 8.7 years); their anthropometric status did not differ from the general population. Approximately one-half of them had at least 1 complication of the disease. Their self-reported global QoL did not differ from that of the general population. However, relations with friends and leisure activities QoL domains were negatively impacted, whereas relations with medical staff, relations with parents, and self-esteem QoL domains were positively impacted. Their proxy (parent)-reported QoL was negatively impacted. Conclusions Young patients affected by IEMRDs present a high rate of clinical complications. Although their proxy (parent)-reported QoL was negatively impacted, their selfreported QoL was variably impacted (both positively and negatively). These results may inform counseling for those who care for affected patients and their families. (J Pediatr 2020;-:1-9). I nborn errors of metabolism (IEMs) 1-4 are a group of inherited genetic disorders characterized by the deficiency or abnormality of an enzyme, its cofactor, or a transporter, involved in various metabolic pathways, leading to either an accumulation or a deficiency of a metabolite. From a pathophysiologic perspective, IEMs can be divided into 3 groups according to the main mechanism leading to the symptoms intoxication-type diseases, in which the metabolic deficit leads to the accumulation of a toxic compound, diseases with deficit in energy production or use, and diseases with disturbance in the synthesis or the catabolism of complex molecules. In the first 2 groups, IEMs are managed with various medications and a lifelong restricted diet (IEMRDs) to either prevent/minimize the intoxication or to bypass the metabolic block providing an alternative source of energy. This diet may have to be adapted to exogenous circumstances associated with an acute catabolism (eg, fever) that might lead to clinical and biological decompensation. Although individual IEMs are rare or very rare, as a group, IEMs occur in approximately 1 in 800-2500 births. 5,6 Progress in diagnostic and therapeutic strategies has led to the increased survival of patients with IEMs, which are now considered chronic diseases. 7

A 25-year longitudinal analysis of treatment efficacy in inborn errors of metabolism

2008

We report here the results of treatment in a panel of 65 inborn errors of metabolism, obtained in the 25th year of a longitudinal project, first reported in 1983. The phenotypic impact of these 65 diseases was scored before and after treatment using a consistent set of parameters, which we have retained to measure change in clinical phenotype throughout the project. We observed significant improvements in the response to treatment for the disease set as a whole. The number of conditions for which there is no response to treatment has progressively decreased; from 31 in 1983, to 20 in 1993, to 17 in 2008. Concomitantly, there has been an increase in the number of conditions that fully respond to treatment (from 8 in 1983 and 1993, to 20 in 2008), and in those for which there is a partial response. Reasons for improved treatment responses include new small molecules, new enzyme replacement therapies, more conditions that can be treated by organ and cell transplantation, and new experimental approaches to substrate reduction and chaperone assisted therapy. However, the most important and new development was not found in one or other particular therapeutic modality but in the access to new knowledge surrounding the individual diseases via the Internet and related resources. Our longitudinal analysis of treatment efficacy for this subset of inborn errors of metabolism continues to constitute a robust and representative assessment of our ability to restore more normal homeostasis in the inborn errors of metabolism.

Perspectives on Dietary Adherence among Women with Inborn Errors of Metabolism

Journal of the American Dietetic Association, 2010

Adherence to highly restrictive diets is critical for women of childbearing age who have inborn errors of metabolism such as phenylketonuria. The purpose of this study was to explore attitudes about diet, barriers to and facilitators of dietary adherence, and experiences with the health care system in promoting dietary adherence among adolescent and adult women with inborn errors of metabolism to identify policy-level interventions to improve adherence. We analyzed the results of four focus groups including a total of 19 women between the ages of 12 and 52 years with phenylketonuria, methylmalonic acidemia, or maple syrup urine disease attending an educational summer camp in 2008. Themes were identified after independent analysis of transcripts. Most participants were highly knowledgeable about their dietary requirements and some could describe their own specific negative experiences of nonadherence. Many reported specific challenges, such as feelings of being different, that they experienced in elementary and middle school. Friends and family play an important role in maintaining dietary adherence. Participants identified one registered dietitian in particular who has played an important supportive role. Insurance coverage for medical foods was a common concern. Most participants identified concerns about transitioning from pediatric to adult medical services. We identified four specific strategies for future evaluation that may improve dietary adherence and health outcomes for women and their potential offspring: symptom-based dietary monitoring for some, educating school officials about medical diets, expanding the role of registered dietitians; and assisting with the transition from pediatric to adult health care providers.

Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism

Molecular Genetics and Metabolism, 2013

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.

Evaluation of Body Composition and Nutritional Status in Patients with Inborn Errors of Metabolism

2020

Inborn errors of metabolism (IEM) are genetically based entities generally characterized by enzyme deficiencies that result in the accumulation of toxic compounds in the body. Children with IEM must follow a special diet restricted in essential nutrients, which can put them at risk for nutritional disorders. This study's objective is to evaluate body composition and nutritional status in patients with IEM and controls, as well as their relationship to lifestyles, food intake, and physical activity. Ninety-nine patients with IEM between the ages of 5 and 19 years and 98 controls by age and sex were analyzed to determine their anthropometric characteristics and body composition using DEXA. Data on personal and family history, socioeconomic status, food intake, and physical activity were collected through validated questionnaires, and nutritional biomarkers were analyzed in all of them. Height z-score was significantly reduced in IEM patients (-0.28 vs. 0.15, p = 0.008), affecting more those with carbohydrate metabolism defects followed by those with amino acid metabolism disorders. Adiposity does not present significant differences in these patients and controls (z-score of the body mass index 0.56 vs. 0.42, p = 0.279). The z-score of waist circumference is higher in patients (-0.08 vs.-0.58, p = 0.005). With regard to bone mineralization, patients present a significantly lower bone mineral density (BMD) (0.89 vs. 1.6, p = 0.001), assuming a higher risk of osteopenia (z-score <-2: 33.3% vs. 20.4%) and osteoporosis (z-score <-2.5: 7.1% vs. 0%), none of which has presented fractures. There was a significant positive correlation between natural protein intake and BMD. Among the analytical studies, the low levels of selenium and high levels of folate stand out, particularly in amino acids metabolism disorders. Our results indicate that patients with IEM in dietary treatment, especially those with disorders of amino acid metabolism, present alterations in body composition, such as low height, a tendency to overweight and obesity, and a decrease in bone mineral density.

Nutrient Intake and Nutritional Status in Adult Patients with Inherited Metabolic Diseases Treated with Low-Protein Diets: A Review on Urea Cycle Disorders and Branched Chain Organic Acidemias

Nutrients

Low-protein diets (LPDs) are the main treatment for urea cycle disorders (UCDs) and organic acidemias (OAs). In most cases, LPDs start in childhood and must be continued into adulthood. The improved life expectancy of patients with UCDs and OAs raises the question of their consequences on nutritional status in adult subjects. As this topic has so far received little attention, we conducted a review of scientific studies that investigated the nutrient intake and nutritional status in adult patients with UCDs and branched chain organic acidemias (BCOAs) on LPD. Methods: The literature search was conducted in PubMed/MEDLINE, Scopus, EMBASE and Google Scholar from 1 January 2000 to 31 May 2020, focusing on nutrient intake and nutritional status in UCD and OA adult patients. Results: Despite protein restriction is recommended as the main treatment for UCDs and OAs, in these patients, protein intake ranges widely, with many patients who do not reach safety levels. When evaluated, micronut...

Nutrition management guideline for maple syrup urine disease: An evidence- and consensus-based approach

Molecular Genetics and Metabolism, 2014

Inborn amino acidopathies Inborn errors of metabolism Inherited metabolic disorders In an effort to increase harmonization of care and enable outcome studies, the Genetic Metabolic Dietitians International (GMDI) and the Southeast Regional Newborn Screening and Genetics Collaborative (SERC) are partnering to develop nutrition management guidelines for inherited metabolic disorders (IMD) using a model combining both evidence-and consensus-based methodology. The first guideline to be completed is for maple syrup urine disease (MSUD). This report describes the methodology used in its development: formulation of five research questions; review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; and expert input through Delphi surveys and a nominal group process. This report includes the summary statements for each research question and the nutrition management recommendations they generated. Each recommendation is followed by a standardized rating based on the strength of the evidence and consensus used. The application of technology to build the infrastructure for this project allowed transparency during development of this guideline and will be a foundation for future guidelines. Online open access of the full, published guideline allows utilization by health care providers, researchers, and collaborators who advise, advocate and care for individuals with MSUD and their families. There will be future updates as warranted by developments in research and clinical practice.

Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years’ experience from a reference center

Orphanet Journal of Rare Diseases, 2018

The use of specialized centers has been the main alternative for an appropriate diagnosis, management and follow up of patients affected by inborn errors of metabolism (IEM). These centers facilitate the training of different professionals, as well as the research at basic, translational and clinical levels. Nevertheless, few reports have described the experience of these centers and their local and/or global impact in the study of IEM. In this paper, we describe the experience of a Colombian reference center for the research, diagnosis, training and education on IEM. During the last 20 years, important advances have been achieved in the clinical knowledge of these disorders, as well as in the local availability of several diagnosis tests. Organic acidurias have been the most frequently detected diseases, followed by aminoacidopathies and peroxisomal disorders. Research efforts have been focused in the production of recombinant proteins in microorganisms towards the development of new enzyme replacement therapies, the design of gene therapy vectors and the use of bioinformatics tools for the understanding of IEM. In addition, this center has participated in the education and training of a large number professionals at different levels, which has contributed to increase the knowledge and divulgation of these disorders along the country. Noteworthy, in close collaboration with patient advocacy groups, we have participated in the discussion and construction of initiatives for the inclusion of diagnosis tests and treatments in the health system.