Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity. The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy. There are currently no consensus guidelines for the diagnosis and management of these patients, resulting in high rates of misdiagnosis, delayed diagnosis, and lack of standardized clinical care. To address this, a group of experts from the United States developed a set of recommendations for the diagnosis and management of all clinical phenotypes of GSD IV, including APBD, to support clinicians and caregivers who provide long-term care for individuals with GSD IV. The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver and heart transplantation, and (e) long-term follow-up care. Remaining knowledge gaps are detailed to emphasize areas for improvement and future research.

Development of the APBD-SQ, a novel patient-reported outcome for health-related quality of life in adult polyglucosan body disease.

Adult polyglucosan body disease (APBD) is a rare autosomal recessive glycogen storage disorder that leads to slowly progressive multi-organ dysfunction in adulthood. A novel disease-specific patient-reported outcome measure was created and administered to assess symptom burden and health-related quality of life (HR-QOL) in APBD. Thirty-six participants between 30 and 79 years of age (83% ≥60 years, 56% male) completed the anonymous questionnaire independently or with a caregiver proxy (75% self-report). Unemployment predicted an 18.3 (95% CI: 2.8, 33.8; p = 0.028) higher composite disease severity score and a 28.8 (95% CI: 8.2, 49.4; p = 0.010) higher composite HR-QOL score. Use of one or more assistive devices also predicted a 29.3 (95% CI: 8.3, 50.4; p = 0.011) higher composite disease severity score and a 41.8 (95% CI: 10.9, 72.8; p = 0.013) higher composite HR-QOL score. Proxy survey completion predicted a 19.4 (95% CI: 4.1, 34.7; p = 0.020) higher composite disease severity score compared to self-report. Older age at survey completion predicted a 27.4 higher composite HR-QOL score (95% CI: 2.5, 52.4; p = 0.039) for participants in their sixties compared to those between 30 and 59 years old. The development of the Adult Polyglucosan Body Disease questionnaire on Symptom burden and health-related Quality of life (APBD-SQ) marks an important stride forward in capturing the patient experience as a tool for disease monitoring and future research.