Assessment of Health-related Quality of Life (HRQoL) and Caregiver Priorities in AP-4 Associated Hereditary Spastic Paraplegia Using the CPCHILD Questionnaire

Abstract

Bi-allelic mutations in genes encoding the subunits of the adaptor protein complex 4 (AP-4) complex lead to childhood-onset forms of hereditary spastic paraplegia (HSP). To systematically document the clinical presentation and natural history of AP-4-related HSP we developed an international registry and natural history study. Not unlike in cerebral palsy, motor symptoms in AP-4-HSP are accompanied by developmental delay and intellectual disability, impaired speech and language development, seizures, and secondary musculoskeletal problems. It is important to understand health related quality of life (HRQoL) and caregiver perspectives to inform shared medical decision making and for developing treatment guidelines and interventional trials. HRQoL measures are complementary to the assessment of clinical disease severity and it is important to establish if correlation exists. To address this gap, we aim to assess the HRQoL in families with AP-4-HSP using the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire. We chose the CPCHILD questionnaire as it has been previously used for other neurological diseases in children, mainly cerebral palsy, and has international accreditation. The questionnaire focuses on the child’s health, comfort, and well-being, and about caring for the individual’s needs. It is important to measure the quality of life in children with disabilities, such as HSP, as there is currently no cure for this illness and the condition is lifelong. This information may assist with medical decision making and anticipatory guidance. Here, we collect and analyze data of HRQoL in relation to clinical manifestations and disease severity. The objective is to describe HRQoL in families with AP-4-HSP and to explore correlations with other clinical outcomes collected through the natural history study. In summary, our results highlight a reduced HRQoL in AP-4-HSP patients and the standardized assessment of caregiver’s priorities identified several domains and areas that are pertinent to the HRQoL in these patients.