Search

Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors of metabolism (IEM). Precision-cut liver slices (PCLS) represent a promising model for studying glucose production ex vivo. This study quantified the net glucose production of human and murine PCLS in the presence of different gluconeogenic precursors. Dihydroxyacetone-supplemented slices from the fed mice yielded the highest rate, further stimulated by forskolin and dibutyryl-cAMP. Moreover, using 13C isotope tracing, we assessed the contribution of glycogenolysis and gluconeogenesis to net glucose production over time. Pharmacological inhibition of the glucose 6-phosphate transporter SLC37A4 markedly reduced net glucose production and increased lactate secretion and glycogen storage, while glucose production was completely abolished in PCLS from glycogen storage disease type Ia and Ib patients. In conclusion, this study identifies PCLS as an effective ex vivo model to study hepatic glucose production and opens opportunities for its future application in IEM research and beyond. Ex vivo precision-cut liver slices allow glucose production quantification to model glycogen storage disease and inborn errors of metabolism. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to evaluate the efficacy and outcomes of renal replacement therapy (RRT) in pediatric patients with metabolic diseases, specifically focusing on the impact of hemodialysis (HD) and peritoneal dialysis (PD) on clinical parameters, toxin reduction, and long-term survival. Methods: This retrospective study included 10 pediatric patients (eight females and two males) treated at a pediatric nephrology department between 2020 and 2023. Patients diagnosed with metabolic disorders, including maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and glycogen storage disease (GSD), underwent RRT. Clinical data, demographic information, and biochemical parameters were collected and analyzed. Results: Among the patients, 50% were diagnosed with MSUD, 30% with MMA, and 20% with GSD. RRT, including HD and PD, was administered to manage acute metabolic crises. HD was particularly effective in rapidly reducing toxic metabolite levels. Patients treated with HD showed significant reductions in leucine and ammonium levels, with median reductions of 94.5% and 86%, respectively. Overall, 60% of the patients demonstrated long-term survival, highlighting the critical role of RRT in managing metabolic crises. In conclusion, RRT, including HD and PD, is crucial in managing pediatric metabolic disorders by effectively reducing toxic metabolite levels and improving clinical outcomes. Conclusions: The results of this study are consistent with previous research, highlighting the critical role of RRT in the acute management of metabolic crises and supporting its adoption as a standard treatment method. [ABSTRACT FROM AUTHOR]

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4 years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable. [ABSTRACT FROM AUTHOR]

Clinical pathway recommendations (CPR) are based on existing guidelines and deliver a short overview on how to deal with a specific diagnosis, resulting therapy and follow-up. In this paper we propose a methodology for developing CPRs for Pompe disease, a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. The CPR document was developed within the activities of the MetabERN, a non-profit European Reference Network for Metabolic Diseases established by the European Union. A working group was selected among members of the MetabERN lysosomal storage disease subnetwork, with specific expertise in the care of Pompe disease, and patient support group representatives. The working strategy was based on a systematic literature search to develop a database, followed by quality assessment of the studies selected from the literature, and by the development of the CPR document according to a matrix provided by MetabERN. Quality assessment of the literature and collection of citations was conducted according to the AGREE II criteria and Grading of Recommendations, Assessment, Development and Evaluation methodology. General aspects were addressed in the document, including pathophysiology, genetics, frequency, classification, manifestations and clinical approach, laboratory diagnosis and multidisciplinary evaluation, therapy and supportive measures, follow-up, monitoring, and pregnancy. The CPR document that was developed was intended to be a concise and easy-to-use tool for standardization of care for patients among the healthcare providers that are members of the network or are involved in the care for Pompe disease patients. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) normalizes fasting tolerance in glycogen storage disease type (GSD) 1b. However, reported outcomes post‐LT with respect to correction of neutropenia, infection risk and growth are varied. Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have been recently shown to improve neutropenia in GSD1b patients. Methods: In this single‐center retrospective study, we reviewed all children who underwent LT for GSD1b. Neutropenia, dose of granulocyte colony‐stimulating factor (G‐CSF), unplanned hospital attendance, anthropometrics, graft rejection, survival, and the effects of dapagliflozin were analyzed. Data from protocol biopsies obtained at 1, 5, and 10 years post‐LT and immunosuppression levels were collected. Results: Eight children (6 female), all on G‐CSF pre‐transplant, underwent cadaveric LT for GSD1b at median age 3.6 years (IQR 3.3–5.1) with mean follow‐up time of 10.3 years (95% CI 7.5–13.1). Neutrophil count and G‐CSF requirement did not improve post‐LT. Although a reduction in unplanned hospital attendance due to infection (0.98 [95% CI 0.76–1.26] vs. 0.49 [95% CI 0.41 to 0.57] per person‐year, p < 0.01) was observed, gastrointestinal complaints and graft dysfunction accounted for a similar hospitalization burden pre‐ versus post‐LT. Body mass index (BMI) reduced post‐LT (Z‐score 1.47 [95%CI 0.39–2.23] vs. 0.56 [95% CI −0.74 to 1.45], p = 0.02), with no significant change in height. Although all children and grafts have survived, 75% of recipients developed rejection, despite adequate immunosuppression levels, with two children having been found to have developed significant fibrosis on their 5‐year protocol biopsy. Although dapagliflozin allowed cessation of G‐CSF, no improvement in neutrophil count was observed. Despite this, a reduction in gastrointestinal and infection‐related morbidity was noted following dapagliflozin. Conclusion: Although LT normalizes fasting tolerance in GSD1b and reduces hospital attendance due to infection, morbidity from infection and gastrointestinal manifestations persist. Children in our cohort experienced high rates of rejection necessitating titration of immunosuppression to balance risk of infection against organ rejection. Future studies should investigate whether early introduction of SGLT2 inhibitors post‐LT impact morbidity in this group. [ABSTRACT FROM AUTHOR]

Hepatocellular adenomas (HCA) are acquired focal liver lesions, that occur mainly in young-to-middle-aged women who are on long-term estrogen-containing contraceptives or young men after prolonged use of anabolic steroids. Furthermore, distinct underlying diseases, such as obesity, metabolic dysfunction-associated steatotic liver disease, glycogen storage disease, etc. are considered risk factors. The 2017 Bordeaux classification, in particular Nault et al, divided HCAs into eight subtypes according to their pheno- and genotypic characteristics. This includes HCAs with hepatocyte-nuclear-factor (HNF1-alpha mutation), HCAs with β-catenin mutation, and HCAs without either of these genetic mutations, which are further subdivided into HCAs with and without inflammatory cells. HCAs should no longer be classified as purely benign without histologic workup since three of the eight subtypes are considered high-risk lesions, requiring adequate management: malignant transformation of the pure (ßex3-HCA) and mixed inflammatory/β-catenin exon 3 (ßex3-IHCA) adenomas, as well as potential bleeding of the sonic hedgehog HCA and pure (ßex7/8-HCA) and mixed inflammatory/β-catenin exon 7/8 (ßex7/8-IHCA). Elective surgery is recommended for any HCA in a male, or for any HCA exceeding 5 cm. Although MRI can classify up to 80% of adenomas, if findings are equivocal, biopsy remains the reference standard for adenoma subtype. [ABSTRACT FROM AUTHOR]

Solute carrier family 37 member 4 (SLC37A4) is known to regulate glucose-6-phosphate transport from cytoplasm to the lumen of the endoplasmic reticulum, which serves to maintain glucose homeostasis. Glycogen storage disease type 1b (GSD1b) is caused by a mutation of SLC37A4, leading to a glycogenolysis defect. Although GSD1b cases are known to be complicated by periodontitis, the etiological molecular basis remains unclear. The present study investigated the effects of SLC37A4 on gingival barrier function. Examinations of immortalized human gingival epithelial (IHGE) cells showed SLC37A4 localized in the endoplasmic reticulum. SLC37A4 knockout decreased expression of JAM1, a tight junction-related protein, in IHGE cells. Using in silico analysis to investigate potential transcription factor binding sites, H6 family homeobox 3 (HMX3) was shown to be related to JAM1 expression. In HMX3-knockdown IHGE cells, JAM1 expression was markedly suppressed. Furthermore, HMX3 was scarcely detected in SLC37A4-knockout cells, while HMX3 overexpression restored JAM1 expression in those cells. Finally, using a three-dimensional multilayered gingival epithelial tissue model, knockout of SLC37A4 was also found to increase permeability to lipopolysaccharide and peptidoglycan, which was dependent on JAM1 expression. Specific downregulation of HMX3 by SLC37A4 and the consequent decrease in JAM1 expression provides findings indicating a molecular basis for the reduction in barrier function of gingival epithelial tissues in GSD1b cases. [ABSTRACT FROM AUTHOR]

Background: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life. Case presentation: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene. Conclusion: This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease. [ABSTRACT FROM AUTHOR]

Introduction and methods: Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease. Results: Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease. Discussion and conclusion: Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings. [ABSTRACT FROM AUTHOR]

AbstractBackground: Isoorientin (ISO), a flavone C-glycoside, is a glycogen synthase kinase 3β (GSK3β) substrate-competitive inhibitor. ISO has potential in treatment of Alzheimer’s disease (AD). An excessive activation of GSK3β can lead to neuroinflammation causing neuronal damage. Microglia cells, as resident immune cells of the central nervous system, mediate neuroinflammation. Here, we studied the effects of ISO on microglial activation to alleviate neuroinflammation.Methods: Effects of ISO were observed upon the stimulation of mouse microglia BV2 or SIM-A9 cells by lipopolysaccharide (LPS). Lithium chloride (LiCl) was the positive control as a GSK3β inhibitor. The release of TNF-α and NO were analyzed by ELISA and Griess assays, while expressions of COX-2, Iba-1, BDNF, GSK3β, NF-κB p65, IκB, Nrf2 and HO-1 were detected by Western blotting. In the co-culture model of SIM-A9 cells and differentiated SH-SY5Y human neuroblastoma cells, effects of ISO on microglia-mediated neuronal damage were evaluated with the MTS assay.Results: ISO significantly inhibited the production of TNF-α (p < 0.01), NO (p < 0.001) and the expression of COX-2 (p < 0.01) and Iba-1 (p < 0.05) induced by LPS, and increased BDNF. The cell viability of SH-SY5Y was inhibited by LPS in the co-culture, which was prevented by ISO pretreatment. ISO increased the expression of p-GSK3β (Ser9), IκB and HO-1 in the cytoplasm, decreased NF-κB p65 and increased Nrf2 in the nucleus compared with the LPS group.Conclusion: ISO attenuated the activation of microglia through regulating the GSK3β, NF-κB and Nrf2/HO-1 signaling pathways to exert neuroprotection. [ABSTRACT FROM AUTHOR]

Glycogen storage diseases (GSDs) are abnormally inherited glycogen metabolism mainly affecting the liver, muscles, and heart. Deficiency of proteins involved in glycogen metabolism caused by genetic mutations are responsible for different subtype of GSDs. However, there are still some challenges in diagnosing GSD. This study includes 39 suspected GSDs patients from unrelated families in China. Next‐generation sequencing (NGS) was used to investigate the reason for their diseases at the genetic level. Finally, all 39 patients were diagnosed with GSDs, including 20 GSD‐Ia, 4 GSD‐VI, and 15 GSD IX (12 GSD‐IXa patients and 3 GSD‐IXb patients). Thirty‐two mutations in G6PC1, PYGL, PHKA2, and PHKB genes were identified, with 14 of them being novel variants. The pathogenicity of novel variants was classified according to ACMG guildlines and predicted by in slico algorithms. Mutations p.L216L and p.R83H in G6PC1 gene may be the hot spot mutation in Chinese. Hearing impairment is a rare clinical feature of GSD Ia, which has also been observed in our cohort. The severity of GSD VI and IX was indicated by our patients. Close follow‐up should be applied to GSD VI and IX patients. Our findings provided evidence for building the phenotype–genotype of GSDs and expanded the mutation spectrum of related genes. [ABSTRACT FROM AUTHOR]

• Most individual neuromuscular disorders are rare, but as a group they are not. • Epidemiological data regarding these disorders, especially incidence, is scarce. • Incidence is underrated whilst just as important as prevalence to describe a disease. • This study researched neuromuscular disorders predominantly diagnosed in adult life. • We provide 15 capture-recapture incidence rates, including 9 previously unavailable. Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the psychometric properties of the EQ-5D (3L and 5L) and SF-6Dv2 in a group of Chinese patients with late-on Pompe disease (PD), and compare their performance in this patient group. Methods: The data used in this study were obtained from a web-based and cross-sectional survey conducted in China. All participants completed the 3L, 5L, and SF-6Dv2. Information about their sociodemographic status and health conditions was also collected. The measurement properties were assessed by examining ceiling and floor effects, evaluating convergent validity, known-group validity, and test–retest reliability (Intraclass correlation coefficient [ICC] and Gwet's AC). Results: A total of 117 PD patients completed the questionnaire. All dimensions of the 3L showed strong ceiling effects, ranging between 17.1 and 42.7%. All three measures showed good test–retest reliability, with ICC values ranging from 0.85 to 0.87. The Gwet's AC values showed that four out of five dimensions of the 3L showed very good agreement. All hypothesized correlations between the 3L, 5L, SF-6Dv2, and items of WHODAS were supported, indicating satisfactory convergent validity. The 5L showed stronger correlations (|r|= 0.53–0.84) with WHODAS than the other two measures. The outcomes of ANOVA indicated that the 5L had higher F-statistics than the 3L and SF-6Dv2, indicating a stronger discriminant ability to differentiate most condition groups. Conclusion: The 5L demonstrates lower ceiling and floor effects, higher discriminant ability, and better convergent validity than the SF-6Dv2 and 3L in patients with PD. In addition, the 5L may generate a larger utility gain compared to the other two instruments when conducting cost-effectiveness analysis. [ABSTRACT FROM AUTHOR]

Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD. [ABSTRACT FROM AUTHOR]

Glycogen Storage Disease Type VII (GSD VII) is a rare glycogen metabolism disorder resulting from mutations in the PFKM gene, inherited in an autosomal recessive manner. It is characterized by exercise intolerance, muscle cramps, myoglobinuria, compensatory hemolysis, and later onset de novo myasthenia and mild myopathy, contributing to its clinical heterogeneity and diagnostic challenges. Here, we report a rare case of a 17-year-old Chinese woman exhibiting substantial muscle weakness and compensated hemolysis. Muscle biopsies showed glycogen deposition, and blood tests showed hyperuricemia and significantly elevated creatine kinase. Whole genome sequencing (WGS) and whole exome sequencing (WES) identified two compound heterozygous mutations in the PFKM (NM_000289.6) gene: c.626G>A and c.1376G>A in exons 7 and 15, respectively. According to the clinical presentation, diagnostic examination, and WES results, the patient was finally diagnosed with GSDVII. The discovery of these two new PFKM mutations expands the genetic spectrum, and understanding the clinical manifestations of these mutations is critical to preventing diagnostic delays and timely intervention and treatment. [ABSTRACT FROM AUTHOR]

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl, enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl−/−. We used open field, grip strength, and rotarod tests for evaluating GHF-201's effects on locomotion, a biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl−/− mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo. [ABSTRACT FROM AUTHOR]

The article discusses the use of ChatGPT, a large language model created by OpenAI, to generate fake medical reports. The authors highlight the potential ethical concerns and challenges posed by AI-generated content in the field of healthcare. They present a case report of a fictitious disease called "Ikusaka disease" to demonstrate how easily ChatGPT can produce plausible yet medically inaccurate texts. The authors emphasize the need for improved validity and responsibility in the outputs of language models and call for high ethical standards among scientists using generative AI. They also discuss the importance of developing methods for detecting fake reports in peer review and publishing processes. [Extracted from the article]

Glycogen debranching enzyme is a single polypeptide with distinct catalytic sites for 4-α-glucanotransferase and amylo-α-1,6-glucosidase. To allow phosphorylase to degrade the inner tiers of highly branched glycogen, 4-α-glucanotransferase converts the phosphorylase-limit biantennary branch G-G-G-G-(G-G-G-G↔)G-G- (G: d -glucose, hyphens: α-1,4-linkages; double-headed arrow: α-1,6-linkage) into the G-G-G-G-(G↔)G-G- residue, which is then subjected to amylo-α-1,6-glucosidase to release the remaining G↔ residue. However, while the essential side-chain structure of the 4-α-glucanotransferase donor substrate has been determined to be the G-G-G-G↔ residue (Watanabe, Y. et al. (2008) J. Biochem. 143 , 435–440), its essential main-chain structure remains to be investigated. In this study, we probed the 4-α-glucanotransferase donor-binding region using novel fluorogenic dextrins G m -(G4↔)G-G n -F (F: 1-deoxy-1-[(2-pyridyl)amino]- d -glucitol) and maltohexaose (G6) as the donor and acceptor substrates, respectively. 4-α-Glucanotransferase exhibited maximum activity towards G4-(G4↔)G-F and G4-(G4↔)G-G-F, indicating that recognition of the G4-(G4↔)G-moiety was essential for full enzyme function. Notably, when the 4-α-glucanotransferase activity towards G4-(G4↔)G-G-F was taken as unity, those towards nonbranching dextrins were < 0.001. This indicated that the disproportionation activities towards maltooligosaccharides (G m ) are abnormal behaviours of 4-α-glucanotransferase. Notably, however, these activities have been traditionally measured to identify the 4-α-glucanotransferase mutations causing glycogen storage disease type III. This study provides a basis for more accurate identification. [ABSTRACT FROM AUTHOR]

Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.g., hypothalamic‑pituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment. Being aware of the endocrine abnormalities occurring in hepatic GSDs is essential (1) to provide optimized medical care to this group of individuals and (2) to drive research aiming at understanding the disease pathophysiology. In this review, a thorough description of the endocrine manifestations in individuals with hepatic GSDs is presented, including pathophysiological and clinical implications. [ABSTRACT FROM AUTHOR]