Insurance Reimbursement for Special Foods and Phenylalanine Levels in Patients With PKU in China.

Importance: Recent changes in China's social medical insurance reimbursement policy have impacted the financial burden of patients with phenylketonuria (PKU) for special foods. However, whether this policy change is associated with their blood phenylalanine (PHE) concentration is unclear. Objective: To investigate the association between the reimbursement policy and blood PHE concentration in patients with PKU. Design, Setting, and Participants: This cohort study measured the blood PHE concentrations of 167 patients with PKU across 4 newborn screening centers in China from January 2018 to December 2021. The reimbursement policy for special foods for patients with PKU at 2 centers was canceled in 2019 and restored from 2020 onwards. In contrast, the other 2 centers consistently implemented the policy. Data were analyzed from September 10 to December 6, 2023. Exposures: The implementation and cancelation of the reimbursement policy for special foods of patients with PKU. Main Outcomes and Measures: The blood PHE concentration was regularly measured from 2018 to 2021. A 1-sided Z test was used to compare the mean of the blood PHE concentration between different years. Results: Among 167 patients with PKU (mean [SD] age, 84.4 [48.3] months; 87 males [52.1%]), a total of 4285 measurements of their blood PHE concentration were collected from 2018 to 2021. For patients at the center that canceled the reimbursement policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (5.73) mg/dL, significantly higher than 4.84 (4.11) mg/dL in 2018 (P < .001), 5.06 (5.21) mg/dL in 2020 (P = .006), and 4.77 (4.04) mg/dL in 2021 (P < .001). Similarly, for patients at the other center that canceled the policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (3.43) mg/dL, significantly higher than 5.34 (3.45) mg/dL in 2018 (P = .03), 5.13 (3.15) mg/dL in 2020 (P = .003), and 5.39 (3.46) mg/dL in 2021 (P = .03). On the contrary, no significant difference was observed between any of the years for patients at the 2 centers that consistently implemented the policy. Conclusions and Relevance: In this cohort study of patients with PKU from multiple centers, the implementation of the reimbursement policy for special foods was associated with controlling the blood PHE concentration. Special foods expenditure for patients with PKU should be included in the scope of long-term social medical insurance reimbursement.

Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes.

Embryonic stem cells (ESCs) are pluripotent stem cells with the ability to self-renew and to differentiate into any cell types of the 3 germ layers. Recent studies have demonstrated that there is a strong connection between mitochondrial function and pluripotency. Here, we report that methyltransferase like (Mettl) 17, identified from the clustered regularly interspaced short palindromic repeats knockout screen, is required for proper differentiation of mouse embryonic stem cells (mESCs). Mettl17 is located in mitochondria through its N-terminal targeting sequence and specifically interacts with 12S mitochondrial ribosomal RNA (mt-rRNA) as well as small subunits of mitochondrial ribosome (MSSUs). Loss of Mettl17 affects the stability of both 12S mt-rRNA and its associated proteins of MSSUs. We further showed that Mettl17 is an S-adenosyl methionine (SAM)-binding protein and regulates mitochondrial ribosome function in a SAM-binding-dependent manner. Loss of Mettl17 leads to around 70% reduction of m4C840 and 50% reduction of m5C842 of 12S mt-rRNA, revealing the first regulator of the m4C840 and indicating a crosstalk between the 2 nearby modifications. The defects of mitochondrial ribosome caused by deletion of Mettl17 lead to the impaired translation of mitochondrial protein-coding genes, resulting in significant changes in mitochondrial oxidative phosphorylation and cellular metabolome, which are important for mESC pluripotency.-Shi, Z., Xu, S., Xing, S., Yao, K., Zhang, L., Xue, L., Zhou, P., Wang, M., Yan, G., Yang, P., Liu, J., Hu, Z., Lan, F. Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes.