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Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disorder of PANK2, which enables mitochondrial synthesis of coenzyme A. Its loss causes neurodegeneration with iron accumulation primarily in motor-related brain areas. Symptoms include dystonia, parkinsonism, and other disabilities. PKAN has been categorized as classic PKAN, with an age of onset ≤ 10 years, rapid progression, and early disability or death; and atypical PKAN, with later onset, slower progression, generally milder, and more diverse symptom manifestations. Available treatments are mostly palliative. Information on the lived experience of patients with PKAN and their caregivers or on community-level disease burden is limited. It is necessary to engage patients as partners to expand our understanding and improve clinical outcomes. This patient-oriented research study used multiple-choice and free-form question surveys distributed by patient organizations to collect information on the manifestations and disease burden of PKAN. It also assessed respondents' experiences and preferences with clinical research to inform future clinical trials. Results: The analysis included 166 surveys. Most respondents (87%) were parents of a patient with PKAN and 7% were patients, with 80% from Europe and North America. The study cohort included 85 patients with classic PKAN (mean ± SD age of onset 4.4 ± 2.79 years), 65 with atypical PKAN (13.8 ± 4.79 years), and 16 identified as "not sure". Respondents reported gait disturbances and dystonia most often in both groups, with 44% unable to walk. The classic PKAN group reported more speech, swallowing, and visual difficulties and more severe motor problems than the atypical PKAN group. Dystonia and speech/swallowing difficulties were reported as the most challenging symptoms. Most respondents reported using multiple medications, primarily anticonvulsants and antiparkinsonian drugs, and about half had participated in a clinical research study. Study participants reported the most difficulties with the physical exertion associated with imaging assessments and travel to assessment sites. Conclusions: The survey results support the dichotomy between classic and atypical PKAN that extends beyond the age of onset. Inclusion of patients as clinical research partners shows promise as a pathway to improving clinical trials and providing more efficacious PKAN therapies. [ABSTRACT FROM AUTHOR]

Summary: In this meta-analysis, we analyzed 9 cross-sectional studies for an association between type 1 diabetes mellitus (T1DM) and bone mineral density (BMD) in children. We found that BMD Z-scores were significantly reduced in children with T1DM. Introduction: Recent cross-sectional studies have examined how T1DM influences bone health in children and adolescents, but the relationship between T1DM and BMD remains unclear due to conflicting reports. Methods: In this meta-analysis, we systematically searched PubMed, Cochrane library, and Web of Science databases (for publications through March 12, 2020), and calculated weight mean difference (WMD) along with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was evaluated using the I2 method. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Results: Data were analyzed from 9 eligible studies, including a total of 1522 children and adolescents. These data were tested for an association between T1DM and BMD. This analysis found a significant decrease in BMD Z-score in the whole body (pooled WMD, − 0.47, 95% CI, − 0.92 to − 0.02, I2 = 80.2%) and lumbar spine (pooled WMD, − 0.41, 95% CI, − 0.69 to − 0.12, I2 = 80.3%) in children and adolescents with T1DM, which was consistent in published studies from Asia and South America, but inconsistent in the North America and Europe. Importantly, the differences in BMD Z-scores were independent of age, level of glucose control (HbA1c), and prepubertal stage. Sensitivity analyses did not modify these findings. Funnel plot and the Egger test did not reveal significant publication bias. Conclusion: This meta-analysis suggests that T1DM may play a role in decreasing BMD Z-scores in the whole body and lumbar spine in children. [ABSTRACT FROM AUTHOR]