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Abstract Introduction Rare genetic neurodevelopmental disorders and intellectual disability (ID), collectively called genetic ID (GID), can profoundly impact daily functioning and overall well-being of affected individuals. To improve our understanding of the impact of GID and advancing both care and research, measuring relevant patient reported outcomes (PROs) is crucial. Currently, various PROs are measured for GID. Given the shared comorbidities across disorders, we aim to develop a generic core PRO set for children and adults with GID. Methods and results Developing the generic core PRO set entails the following steps: 1) providing an overview of potentially relevant PROs by scoping reviews and qualitative research; 2) integrating and conceptualizing these PROs (i.e., describing the content of the PROs in detail) into a pilot generic core PRO set; and 3) prioritizing relevant PROs by a European Delphi survey and consensus meetings. Conclusions This protocol presents the steps for developing a generic core PRO set for children and adults with GID. The next step involves selecting suitable patient reported outcome measures (PROMs) to adequately measure these PROs: the generic core PROM set. This generic core PROM set needs validation in the GID population, and eventually implementation in care and research, facilitating the aggregation and analysis of PRO data and guaranteeing continuous integration of the patient perspective in both care and research.

Abstract Background Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.