Acute intoxication‐type inborn errors of metabolism (IT‐IEM) such as urea cycle disorders and non‐acute IT‐IEM such as phenylketonuria have a major impact on paediatric patients' life. Patients have to adhere to a strict diet but may face neurocognitive impairment and – in acute diseases – metabolic decompensations nevertheless. Research on the subjective burden of IT‐IEM remains sparse. Studies with appropriate sample sizes are needed to make valid statements about health‐related quality of life (HrQoL) in children and adolescents with IT‐IEM. Six international metabolic centres contributed self‐reports and proxy reports of HrQoL (assessed with the Paediatric Quality of Life Inventory) to the final data set (n = 251 patients; age range 2.3‐18.8 years). To compare HrQoL of the patient sample with norm data and between acute and non‐acute IT‐IEM, t tests were conducted. To examine the influence of child age, sex, diagnosis and current dietary treatment on HrQoL, multiple linear regression analyses were conducted. Self‐reports and proxy reporst showed significantly lower HrQoL total scores for children with IT‐IEM compared to healthy children. Current dietary treatment significantly predicted lower proxy reported total HrQoL. Children with non‐acute IT‐IEM reported significantly lower psychosocial health and emotional functioning than children with acute IT‐IEM. The patient sample showed significantly impaired HrQoL and a diet regimen remains a risk factor for lower HrQoL. Differences in HrQoL between acute and non‐acute IT‐IEM subgroups indicate that factors beyond symptom severity determine the perception of disease burden. Identifying these factors is of crucial importance to develop and implement appropriate interventions for those in need.

BackgroundIn recent decades, considerable progress in diagnosis and treatment of patients with intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders (UCD), organic acidurias (OA), maple syrup urine disease (MSUD), or tyrosinemia type 1 (TYR 1) has resulted in a growing group of long-term survivors. However, IT-IEM still require intense patient and caregiver effort in terms of strict dietetic and pharmacological treatment, and the threat of metabolic crises is always present. Furthermore, crises can affect the central nervous system (CNS), leading to cognitive, behavioural and psychiatric sequelae. Consequently, the well-being of the patients warrants consideration from both a medical and a psychosocial viewpoint by assessing health-related quality of life (HrQoL), psychological adjustment, and adaptive functioning. To date, an overview of findings on these topics for IT-IEM is lacking. We therefore aimed to systematically review the research on HrQoL, psychological adjustment, and adaptive functioning in patients with IT-IEM.MethodsRelevant databases were searched with predefined keywords. Study selection was conducted in two steps based on predefined criteria. Two independent reviewers completed the selection and data extraction.ResultsEleven articles met the inclusion criteria. Studies were of varying methodological quality and used different assessment measures. Findings on HrQoL were inconsistent, with some showing lower and others showing higher or equal HrQoL for IT-IEM patients compared to norms. Findings on psychological adjustment and adaptive functioning were more consistent, showing mostly either no difference or worse adjustment of IT-IEM patients compared to norms. Single medical risk factors for HrQoL, psychological adjustment, or adaptive functioning have been addressed, while psychosocial risk factors have not been addressed.ConclusionData on HrQoL, psychological adjustment, and adaptive functioning for IT-IEM are sparse. Studies are inconsistent in their methodological approaches, assessment instruments and norm populations. A disease-specific standard assessment procedure for HrQoL is not available. Psychosocial risk factors for HrQoL, psychological adjustment, or adaptive functioning have not been investigated. Considering psychosocial variables and their corresponding risk factors for IT-IEM would allow evaluation of outcomes and treatments as well as the planning of effective social and psychological interventions to enhance the patients’ HrQoL.

Introduction: This study is part of the "European network and registry for intoxication type metabolic diseases" (E-IMD) project. Intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders (UCD) and organic acidurias (OA) have a major impact on patients' lives. Patients have to adhere to strict diet and medication and may suffer from metabolic crises and neurocognitive impairment. Disease-specific health-related quality of life (HrQoL) assessment questionnaires are the method of choice to estimate the subjective burden of a Communicated by: Pascale de Lonlay "Peter Burgard," "Markus A. Landolt," and "Martina Huemer" are contributed equally to this project. Electronic supplementary material:The online version of this chapter