肝型糖原病

BACKGROUND: Glycogen Storage Disease Type I (GSD I) is an inherited metabolic disorder characterized by impaired hepatic glucose production due to defects in gluconeogenesis and glycogenolysis. Two subtypes are recognized: GSD Ia (G6PC) and GSD Ib (SLC37A4). Genotype-phenotype correlations and long-term outcomes in Southeast Asia remain insufficiently characterized. This study aimed to describe the clinical, biochemical, and molecular features of Vietnamese children with GSD I and evaluate treatment outcomes . METHODS: Twenty-four patients from 19 families diagnosed at the Vietnam National Children's Hospital between 2016 and 2025 were included. All underwent genetic testing. Clinical characteristics and laboratory parameters were collected at diagnosis and during follow-up . RESULTS: Twelve distinct variants were identified, including eight in G6PC and four in SLC37A4, with one novel variant (c.1193G > A). The most common G6PC variants were c.518 T > C, c.356 A > T, and c.648G > T, while c.706_708delGTG predominated in SLC37A4. The median age at symptom onset was 4 months, and 70% of patients presented with hepatomegaly. Elevated liver enzymes and lactate levels were observed in all cases, and 88.2% had hypertriglyceridemia. Dietary adherence was generally poor despite uncooked cornstarch therapy. During follow-up, patients with GSD Ia developed complications including short stature, hepatic adenoma, pancreatitis, hypertension, kidney stones, and cirrhosis, while all GSD Ib patients experienced neutropenia and required empagliflozin for recurrent infections . CONCLUSION: Hepatomegaly with elevated liver enzymes, lactate, and triglycerides is a common presentation of GSD I. Variant distribution may differ across populations, and complications can occur at any age.

Background/Objectives: Hepatic glycogen storage diseases (GSDs) are rare inherited metabolic disorders requiring lifelong nutritional management and strict metabolic control, which may adversely affect the health-related quality of life (HRQoL). This study aimed to evaluate the HRQoL in children with hepatic GSD using both child and parent reports, compare findings with normative data, and explore associations with biochemical, anthropometric, and nutritional management-related parameters. Methods: The study included 23 children with hepatic GSD and their parents. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale. Child and parent reports were compared with normative data for healthy and chronically ill children. Agreement between child and parent reports was evaluated with intraclass correlation coefficients, and exploratory associations between variables were assessed using partial Spearman correlation analyses. Results: Total and most subscale PedsQL scores reported by both children and parents were significantly lower than those of healthy peers and children with chronic diseases (p < 0.05). Parents reported lower HRQoL scores than children, particularly in psychosocial, social, and school functioning domains, with low to moderate agreement between reports. Exploratory analyses suggested that body composition and nutritional treatment burden indicators were correlated with selected HRQoL domains. Conclusions: Children with hepatic GSD experience impaired HRQoL from both child and parent perspectives. Integrating HRQoL assessment into routine clinical and nutritional follow-up may help identify unmet psychosocial and dietary support needs and support more individualized nutritional management in children with hepatic GSD.

Pompe disease (PD) results from lysosomal acid α-glucosidase (GAA) deficiency, causing lysosomal glycogen accumulation in cardiac and skeletal muscles. We previously characterized a murine model carrying the orthologous human infantile-onset PD (IOPD) pathogenic variant, c.1826dupA (p.Y609*), introduced into the mouse Gaa gene. Compared to wild-type (WT; C57BL/6NJ) controls, Gaac.1826dupA mice exhibit reduced GAA activity and develop early-onset hypertrophic cardiomyopathy-evidenced by increased left ventricular wall thickness and left ventricular mass index (LVMI)- as well as impaired grip strength and gait abnormalities. To benchmark the model's disease fidelity and assess its responsiveness to established therapeutic intervention, Gaac.1826dupA mice received a single retro-orbital dose of AAV2/8-LSPhGAA (2 × 109 vg/g body weight) at postnatal day 12-14. Twelve weeks post-treatment, mice exhibited supraphysiological GAA enzymatic activity in the heart (550% of WT) and liver (400% of WT) with a 93% reduction in cardiac glycogen. No sex-dependent differences in therapeutic efficacy were observed. Echocardiography revealed robust reversal of cardiac pathology, with wall thicknesses and LVMI values approaching WT levels. In contrast to this profound cardiac rescue, skeletal muscle improvements were modest; while forelimb grip strength remained unchanged, automated gait analysis showed benefit limited to hind paw base of support. These findings demonstrate that the Gaac.1826dupA model mirrors the critical cardiomyopathy characteristic of IOPD. While systemic AAV treatment yields definitive cardiac correction, the partial skeletal muscle response highlights a clear need for optimization. Consequently, the Gaac.1826dupA mouse serves as a high-fidelity platform for evaluating next-generation genomic correction strategies targeting both cardiac and refractory neuromuscular manifestations of PD.

OBJECTIVE: This study aimed to investigate the molecular characteristics of T2DM with MASLD in a C57 mouse model, using multi-omics techniques to identify key nutritional metabolites that drive metabolic dysfunction. The goal was to reveal how metabolic disturbances are linked to transcriptional reprogramming, providing a new theoretical basis for nutritional biomarker discovery and targeted metabolic interventions. METHODS: In this study, a mouse model of T2DM with MASLD was established using a high-fat diet (HFD) combined with intraperitoneal injection of low-dose streptozotocin (STZ). The mice were randomly allocated into three groups: a healthy control group, a MASLD-only group (HFD), and a T2DM with MASLD group (HFD + 40 mg/kg STZ, ip). Serum untargeted metabolomic analysis and hepatic transcriptomic sequencing were performed to identify significantly differential metabolites and transcripts between groups, specifically focusing on α-hydroxybutyrate (α-HB) and glycogen synthase 2 (GYS2). Multi-omics data integration was conducted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Pearson correlation analysis. For the validation experiment, both normal mice and T2DM with MASLD mice were further divided into two subgroups, with one subgroup from each cohort receiving α-HB intervention to investigate its effects on GYS2 expression and the progression of T2DM with MASLD. RESULTS: Metabolomic and transcriptomic analyses revealed that α-HB levels were significantly elevated in T2DM with MASLD mice, and this elevation showed a significant correlation with the downregulation of GYS2. Validation experiments demonstrated that, compared with normal mice, the T2DM with MASLD mice induced by a high-fat diet combined with STZ injection exhibited significantly increased fasting blood glucose (13.14 ± 0.44 vs. 5.08 ± 0.30 mmol/L, p < 0.0001), insulin levels (47.41 ± 1.38 vs. 12.38 ± 1.29 μU/mL, p < 0.0001), serum triglycerides (4.75 ± 0.13 vs. 1.27 ± 0.13 mmol/L, p < 0.0001), and hepatic triglycerides (61.97 ± 3.53 vs. 17.13 ± 1.01 mg/g, p < 0.0001), along with elevated inflammatory factors. GYS2 was significantly downregulated in T2DM with MASLD mice. Compared with saline-treated T2DM with MASLD mice, α-HB-treated T2DM with MASLD mice showed a further downregulation of hepatic GYS2 expression (p = 0.0011). Following α-HB intervention, T2DM with MASLD mice showed a further downregulation of hepatic GYS2 expression compared to saline-treated T2DM with MASLD mice (p = 0.0011). This was accompanied by increased fasting blood glucose (14.70 ± 0.37 vs. 13.14 ± 0.44 mmol/L, p = 0.0230) and insulin levels (53.16 ± 0.90 vs. 47.41 ± 1.38 μU/mL, p = 0.0086), as well as reduced hepatic glycogen synthesis (21.60 ± 0.97 vs. 35.34 ± 1.40 mg/mg, p < 0.0001). Concurrently, serum triglycerides (5.63 ± 0.50 vs. 4.75 ± 0.13 mmol/L, p = 0.0160), hepatic triglycerides (70.53 ± 0.69 vs. 61.97 ± 3.53 mg/g, p < 0.0398), and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) (9.69 ± 0.62 vs. 45.70 ± 2.50 ng/L, p = 0.0013) and interleukin-6 (IL-6) (55.87 ± 5.39 vs. 37.68 ± 0.78 ng/L, p = 0.0029) were all significantly elevated. CONCLUSION: This study reveals that α-HB, a metabolite elevated under conditions of nutrient overload and insulin resistance, plays an important role in the progression of T2DM with MASLD. It may contribute to a vicious cycle by impairing hepatic energy storage and flux, likely through affecting the activity and expression of GYS2. This finding provides a nutritional metabolism perspective for understanding the T2DM with MASLD comorbidity and suggests α-HB as a potential target for nutritional strategies or precision nutrition approaches.

Due to its unique metabolism and digestive traits, the common myna (Acridotheres tristis) is particularly susceptible to liver diseases, including iron storage disease (ISD) and hepatic lipidosis. This study, conducted on 29 mynas referred to veterinary centers in Kermanshah, aimed to evaluate correlations between serological findings, radiographic features, and histopathological changes. Blood biochemical and antioxidant parameters were assessed, and liver size measurements were obtained via radiographs in lateral and ventrodorsal positions. Ultrasound-guided fine-needle core biopsies provided tissue samples for histopathological evaluation and disease severity assessment. Results showed that serum cholesterol > 129.5 mg/dL (p = 0.0012) and triglycerides > 55 mg/dL (p = 0.0071) were significantly associated with hepatic lipidosis. The mean Malondialdehyde (MDA) concentration in affected birds was 0.8384 nM, correlating with larger liver sizes. Radiographs indicated liver sizes > 67.45 mm, with receiver operating characteristic (ROC) analysis revealing 83.33% sensitivity and 87.5% specificity for detecting hepatic conditions. Serum ferritin > 1.955 ng/mL was identified as a reliable diagnostic indicator for ISD. However, radiographic liver size alone was insufficient for definitive differentiation between hepatic lipidosis and ISD. Using Periodic Acid-Schiff (PAS) and Prussian blue staining, histopathological examination confirmed lipid and glycogen deposition in hepatic lipidosis and hemosiderin accumulation in ISD, validating the biochemical findings. This study highlights the necessity of multimodal diagnostic approach integrating biochemical, radiological, and histopathological techniques for accurate diagnosis and management of hepatic diseases in mynas.