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Background The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases. Methods At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN’s clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data. Results As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method – 0% missing). Discussion Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.

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

Background Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. The main purpose of this retrospective cohort study was to identify prevalence of inherited neurotransmitter disorders. Methods This retrospective cohort study does not have inclusion criteria; rather included all patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol acetic acid measurements. Patients with CSF neurotransmitter investigations suggestive of an inherited neurotransmitter disorder and patients with normal or non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of single gene disorders. Results There were 154 patients between October 2004 and July 2013. Four patients were excluded due to their diagnosis prior to this study dates. Two major clinical feature categories of patients who underwent lumbar puncture were movement disorders or epilepsy in our institution. Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients). Conclusion Prevalence of inherited neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of the 150 patients (5.3%) had one of the treatable inherited metabolic disorders with favorable short-term neurodevelopmental outcomes, highlighting the importance of an early and specific diagnosis. Whole exome or genome sequencing might shed light to unravel underlying genetic defects of new inherited neurotransmitter disorders in near future.