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

Abstract

Abstract 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.