Patient-reported outcomes and quality of life in PMM2-CDG

Ligęzka, Anna; Mohamed, Anab; Pascoal, Carlota; Ferreira, Vanessa; Boyer, Suzanne; Lam, Christina; Edmondson, Andrew C.; Krzyściak, Wirginia; Golebiowski, Raphael; Perez-Ortiz, Judit; Morava, Éva

doi:10.1016/j.ymgme.2022.04.002

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…Emotional problems and depression were not found to be relevant problems by any of the screening tools. These ndings differ from those reported by Ligezka et al [32]. However, remarkably, a subset of patients with absence of lipodystrophy showed a statistically signi cantly correlation to an increase in the existence of signi cant "Withdrawn/depressed" and also "Affective problems".…”

Section: Discussioncontrasting

confidence: 90%

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

Epifani,

Pujol,

Llorens

et al. 2023

Preprint

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Phosphomannomutase deficiency (PMM2-CDG) causes cerebellar atrophy and presents with ataxia, dysmetria, and intellectual deficits. Despite ongoing therapy development and clinical trials, limited knowledge exists regarding the cognitive and adaptive profile. We evaluated a large cohort assessing the adaptive profile and its association with parental stress, clinical, and molecular characteristics. We recruited 37 individuals, and used validated scales to assess disease severity, behavioral and adaptive functioning, psychopathology and parental stress. Results were compared with clinical features. No significant differences were found based on age or gender. "Daily living skills" was the most affected domain. Patients clinically classified as severe had significantly lower adaptive skill values, as did those with lipodystrophy and inverted nipples. Learning difficulties and scholastic problems were consistently observed. Greater severity in motor cerebellar syndrome, behavioral disturbances and the presence of comorbidities such as hyperactivity, autistic features and moderate-to-severe intellectual disability correlate with higher scores in parental stress. Although not longitudinal, our study indicates either stabilization or no progression in adaptive abilities. Our findings offer validated tools to assess adaptive deficits in PMM2-CDG patients, emphasizing the importance of addressing communication, executive function, daily living skills, autonomy, and their impact on parental stress in clinical monitoring and future therapies.

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Section: Discussioncontrasting

confidence: 90%

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

Epifani,

Pujol,

Llorens

et al. 2023

Preprint

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“…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 ).…”

Section: Discussion Conclusion and Future Perspectivesmentioning

confidence: 99%

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

Pascoal,

Francisco,

Mexia

et al. 2024

Front. Immunol.

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Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG.

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“…Some general patient-reported clinical assessment tools have already been used in clinics for PMM2-CDG, particularly the Goal Attainment Scale and the patient-centred measures from Patient-Reported Outcomes Measurement Information System (PROMIS) [ 32 , 33 ]. However, none of these reflect the most impactful conditions presented by the patients.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…Besides, we believe that the over or underestimation of QoL from proxies can be systematic and therefore, changes across time and following an intervention should be captured. Measuring clinical severity alongside proxy-reports might be a way to ensure their reliability [ 33 ]. However, we cannot discard that a minority of PMM2-CDG patients might be able to express themselves and provide QoL self-ratings.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

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

Pascoal

Ferreira

Teixeira

et al. 2022

Orphanet J Rare Dis

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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.

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Patient-reported outcomes and quality of life in PMM2-CDG

Cited by 15 publications

References 29 publications

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

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

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

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

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