メープルシロップ尿症

OBJECTIVES: To review our use and outcomes of continuous renal replacement therapy (CRRT) for acute metabolic decompensation (hyperammonemia or hyperleucinemia) in infants and children with inborn errors of metabolism (i.e., M), and to identify factors associated with complications and mortality. DESIGN: Retrospective cohort identified using local clinical databases. SETTING: Single-center PICU and neonatal ICU in a tertiary pediatric center in Türkiye. PATIENTS: Thirty-eight children (with 49 CRRT sessions) for urea cycle disorders, organic acidemias, or maple syrup urine disease undergoing treatment between August 2014 and June 2025. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range, IQR) age at CRRT initiation was 1.4 months (IQR 0.16-33.90); CRRT resulted in substantial metabolite reduction (mean change 87.6% for ammonia and 74.8% for leucine). Younger age was associated with more hemodynamic and metabolic complications. Overall mortality was 11 of 38 (28.9% [95% CI, 17-44.8%]). In the 11 episodes of CRRT that ended in death vs. 38 CRRT episodes with survival to discharge, there was a greater proportion with hypophosphatemia: 6 of 11 vs. 8 of 38, percentage difference 33.4% (95% CI, 2.8-59.6%), p value of equals to 0.03. Last, we failed to identify an association between episodes of CRRT by technique (continuous venovenous hemodiafiltration [CVVHDF] vs. dialysis) and mortality: 6 of 21 vs. 5 of 28, mean difference 10.7% (95% CI, -12.4 to 34.3%), p value of equal to 0.38. CONCLUSIONS: In our single-center 11-year experience of using CRRT for metabolic detoxification in critically ill young infants with inborn errors of metabolism, we have found that substantial reductions in ammonia and leucine can be achieved in severe biochemical derangement, irrespective of whether continuous venovenous hemodialysis or CVVHDF was used. Taken together, for us, these findings reinforce our continued practice of timely CRRT as a critical component of acute metabolic crisis management.

OBJECTIVE: Artificial intelligence (AI)-based large language models (LLMs) are increasingly used to support nutrition-related decision-making; however, their ability to generate clinically appropriate dietary plans for inherited protein metabolism disorders remains largely unexplored. This study aimed to perform an exploratory simulation-based benchmarking analysis of AI-generated dietary plans for phenylketonuria (PKU), maple syrup urine disease (MSUD), and propionic acidemia (PPA) using disease-specific metabolic nutrition guidelines. METHODS: Standardized pediatric case scenarios were developed for PKU, MSUD, and PPA. Using identical English-language prompts, ChatGPT-5.3 Pro and Gemini 3 Pro Advanced each generated 3-day dietary plans. Nutrient composition was analyzed using the BeBiS Nutrition Information System and evaluated against Dietary Reference Intakes (DRIs). Disease-specific nutritional targets, including amino acid intake, protein distribution, and energy provision, were benchmarked against recommendations from Genetic Metabolic Dietitians International (GMDI). Nutritional characteristics of the dietary plans generated by the two AI models were compared using exploratory statistical analyses. RESULTS: Both LLMs generated structured dietary plans with generally acceptable overall nutritional characteristics; however, clinically relevant deviations from disease-specific nutritional targets were identified across all three disorders. In the PKU case, both models achieved the recommended phenylalanine range, but neither simultaneously met protein and tyrosine recommendations. In the MSUD case, differences were primarily related to energy provision and branched-chain amino acid targets, while in the PPA case neither model achieved the recommended balance between intact protein and total protein. These findings demonstrated that conventional measures of nutritional adequacy alone were insufficient to determine the clinical appropriateness of AI-generated dietary plans for inherited protein metabolism disorders. CONCLUSION: General-purpose LLMs can generate structured dietary plans for inherited protein metabolism disorders; however, disease-specific metabolic targets are not consistently achieved. Evaluation of AI-generated dietary plans should therefore extend beyond conventional nutritional assessment and incorporate disease-specific benchmarking against established metabolic nutrition guidelines. This study provides a disease-specific benchmarking framework for evaluating AI-generated dietary plans in inherited protein metabolism disorders.

Sarcopenia is increasingly recognized in pediatric chronic diseases, yet its prevalence and determinants in children with intoxication-type inborn errors of metabolism (IEM) have never been investigated. This study aimed to evaluate sarcopenia in this population and to investigate associated metabolic alterations. We conducted a retrospective single-center study including 45 pediatric patients (0-18 years) with maple syrup urine disease (MSUD, 11 pts.), organic acidurias (OA, 22 pts.), or urea cycle defects (UCD, 12 pts.) considered for liver transplantation. Sarcopenia was defined as total psoas muscle area z-score ≤ -2 on CT scan. Anthropometric, dietary, and laboratory parameters were analyzed. Forty percent of patients exhibited sarcopenia, most frequently among OA (54.5%) and UCD (33.3%), and only occasionally in MSUD (18.2%). Sarcopenic children showed lower weight, height, and were more likely to require enteral nutritional support. Plasma levels of essential amino acids, particularly branched-chain amino acids (leucine, isoleucine, valine), histidine, and glutamine, were significantly reduced in sarcopenic patients. Leucine emerged as an independent predictor of sarcopenia (p = 0.016). FGF21 levels were elevated in sarcopenic OA and UCD patients, whereas MSUD patients with higher branched-chain amino acids levels showed lower FGF21, suggesting a role beyond mitochondrial stress signaling. Sarcopenia is common in pediatric patients with severe intoxication-type IEM and is closely linked to essential amino acid deficiencies and altered FGF21 signaling. These monogenic diseases provide unique pathophysiological models for better understanding of sarcopenia. Our findings highlight the need for targeted nutritional and metabolic strategies to preserve muscle mass in these vulnerable patients.

Maple Syrup Urine Disease (MSUD) is caused by a genetic mutation in the branched-chain α-ketoacid dehydrogenase complex, resulting to accumulation of branched-chain amino acids (BCAAs) that affect the central nervous system and cause neurochemical alterations and behavioral changes. In this line, full-spectrum cannabidiol (CBD)-rich oil has emerged as a potential therapeutic strategy. Therefore, this study aims to evaluate the effects of two doses of the compound full-spectrum CBD-rich oil in a BCAA-induced MSUD rat model, against behavioral, cholinergic, inflammatory, and oxidative stress parameters. For this, animals were divided into six groups: control group, CBD 3.5 mg/kg group, CBD 7.5 mg/kg group, BCAA group, BCAA + CBD 3.5 mg/kg group, and BCAA + CBD 7.5 mg/kg group. The treatment was administered over 21 days; after that, the animals were subjected to open-field and object recognition tests. Next, we extracted the cerebral cortex to analyze cholinergic function, inflammation, and oxidative stress. The results show that the open-field test revealed no differences in crossings and rearings across all groups. In object recognition test, control and CBD 3.5 groups showed improved short- and long-term memory compared to training. The CBD 7.5 and BCAA + CBD 3.5 groups showed improvement only in short-term memory. BCAA control and BCAA + 7.5 did not present differences. In the cholinergic system, BCAA control showed decreased choline acetyltransferase (ChAT) activity, which was reversed by CBD treatment at both doses. The BCAA + CBD 7.5 shows increased ChAT activity compared to control group. While acetylcholinesterase (AChE) was reduced in the CBD 7.5 groups and increased in the BCAA control group, both CBDs reversed this increase in BCAA control group. Inflammatory cytokines show increased interleukin-1β in BCAA control group, and the CBD treatment decreases its levels compared to BCAA and saline control groups. Interleukin-6 increases in BCAA control group, and CBD 3.5 reverses it. Tumoral necrosis factor-alpha was reduced in BCAA + CBD 3.5 and BCAA + CBD 7.5 compared to control and BCAA control groups. Further, under oxidative stress, BCAA control increases 2,7-dichlorofluorescein oxidation and thiobarbituric acid levels, which were reversed by CBD treatment. Sulfhydryl content was decreased in CBD 7.5, BCAA control group, BCAA + CBD 3.5, and BCAA + CBD 7.5 compared to control group. Superoxide dismutase activity increased across all groups, whereas catalase activity decreased in the BCAA control group; treatment with CBD 7.5 reversed this reduction. Overall, we conclude that full-spectrum CBD-rich oil shows therapeutic potential for MSUD, although optimal dosing and treatment duration require further investigation.

Amino acid metabolic disorders (AAMs) are a group of inherited metabolic diseases caused by defects in enzymes or transporters involved in amino acid metabolism. This systematic review and meta-analysis aimed to evaluate the incidence, disease spectrum, and regional distribution of AAMs in China. A comprehensive search of PubMed, Embase, Web of Science, and major Chinese databases identified studies published between January 2002 and December 2025. After rigorous screening and quality assessment, 65 studies were included, encompassing 16,757,850 newborns and 2928 confirmed AAM cases. The most prevalent subtypes included hyperphenylalaninemia (HPA), hypermethioninemia (MET), citrin deficiency (CD), citrullinemia type 1 (CTLN1), maple syrup urine disease (MSUD), ornithine transcarbamylase deficiency (OTCD), and tyrosinemia (HT). The pooled incidence of AAMs was estimated at 184.0 (95% confidence interval 155.0-218.0) per million newborns. Significant regional differences were observed in the overall incidence of AAMs, with a higher incidence in northern China than southern China (287.0 vs. 126.0 per million, p < 0.0001). This difference was largely attributable to the substantially higher prevalence of HPA in northern China, whereas other major AAM subtypes showed no significant north-south differences. In contrast, no significant north-south differences were identified for other major subtypes. Additionally, the proportion of tetrahydrobiopterin deficiency (BH4D) among HPA cases was significantly higher in southern China (p < 0.001). These findings provide comprehensive epidemiological evidence on AAMs in China and highlight the importance of region-specific newborn screening strategies.