Patient reported outcomes for phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG): listening to what matters for the patients and health professionals

Abstract

Background Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease. Aim and methods This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients’ QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed. Results Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients’ lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire. Conclusion Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review

“…For instance, collecting patient-reported outcomes and quality of life data would be extremely important to have a holistic perspective on the disease’s impact, particularly in terms of immunological episodes. Namely, in PMM2-CDG, some tools have been pinpointed ( 220 , 221 ).…”

Untangling adaptive functioning of PMM2-CDG across age and its impact on parental stress: a cross-sectional study

“…However, this is the rst study to evaluate the adaptive behavior, functioning and psychopathological pro le of PMM2-CDG patients, something of signi cant concern for families. Intellectual di culties, problems with daily activities and self-direction, along with behavioral disturbances, limit patients' autonomy and negatively impact the quality of life of both patients and their families [12]. There are no validated tools available for the assessment of behavioral and cognitive clinical characteristics.…”

“…However, there is limited research and description of the adaptive functioning and behavioral features of PMM2-CDG, despite existing evidence [3,10], and the urgent need due to the promising therapies that are developing and the clinical trials that are ongoing [11]. Furthermore, recent ndings highlight the importance of addressing neurological and mental health issues from the perspective of patients and caregivers [12], as the condition greatly impacts their quality of life.…”

Untangling adaptive functioning of PMM2-CDG across age and its impact on parental stress: a cross-sectional study

“…However, this is the first study to evaluate the adaptive behavior, functioning and psychopathological profile of PMM2-CDG patients, something of significant concern for families. Intellectual difficulties, problems with daily activities and self-direction, along with behavioral disturbances, limit patients' autonomy and negatively impact the quality of life of both patients and their families 12 . However, the assessment of these clinical behavioral and cognitive characteristics is not typically included in physician evaluations or clinical trial protocols, and no tools have been specifically tested in this patient group.…”