JOURNAL OF INHERITED METABOLIC DISEASE遗传性代谢病杂志
JOURNAL OF INHERITED METABOLIC DISEASE(英文缩写 J INHERIT METAB DIS),ISSN 0141-8955,eISSN 1573-2665,中文译名:遗传性代谢病杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 4.750 | Q2 |
| 2022 | 4.200 | Q1 |
| 2023 | 4.200 | Q1 |
| 2024 | 3.800 | Q2 |
| 2025 | 3.800 | Q2 |
JOURNAL OF INHERITED METABOLIC DISEASE 最新收录文献
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1. Treatment of Fatty Acid Oxidation Disorders Today: Emerging Personalized Treatment Strategies.
PMID:日期:2026-09-01The first international guideline on treatment and management of long-chain fatty acid oxidation disorders has been published and demonstrates little scientific evidence for many of the treatment decisions. However, it is a substantial achievement to harmonize treatment and to define the remaining challenges. We here deliver some thoughts on this guideline and highlight the tremendous effort to reach this international consensus.
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2. International Guideline on the Diagnosis, Treatment, and Monitoring of Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD).
PMID:日期:2026-09-01Long-chain fatty acid oxidation disorders (LC-FAOD) are rare inherited defects of mitochondrial β-oxidation that impair energy generation during fasting or metabolic stress. Clinical manifestations range from neonatal hypoketotic hypoglycemia and cardiomyopathy to hepatopathy, recurrent rhabdomyolysis, and chronic myopathy. Although newborn screening (NBS) enables early detection, management remains inconsistent due to limited evidence, broadening phenotypic spectrum, and regional practice variation. An international multidisciplinary workgroup of 34 members, including clinicians, nurses, dietitians, and patient representatives, systematically reviewed the literature (1990-2022) using PubMed, Embase, and Web of Science. Evidence was graded using an adapted Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and consensus was achieved through a modified Delphi-Nominal Group-Delphi methodology, with agreement defined as ≥ 75%. Especially when evidence was low, expert consensus was the basis for this guideline. Recommendations address diagnosis, dietary management, fasting tolerance, use of medium-chain fat sources, exercise and illness protocols, pregnancy care, and long-term monitoring. Evidence quality ranged from very low to moderate. Strong consensus was reached for critical clinical interventions. Standardized approaches for diagnostic work-up, management during metabolic stress, and follow-up monitoring were developed to promote uniform care across age groups, disease groups, and phenotypic severity. This international guideline integrates available evidence and expert consensus to provide standardized recommendations for diagnosis, treatment and lifelong management of LC-FAOD. They aim to harmonize clinical practice, improve patient outcomes, and support global implementation of evidence-based metabolic care.
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3. {"_":"L-Carnitine Prevents Lipopolysaccharide-Induced Inflammatory Response, Microglia Activation and Neuronal Damage in Cerebral Cortex, as Well as Neuromotor Development Delay in Neonatal Glutaryl-CoA Dehydrogenase Deficient (Gcdh) Mice.","sup":["-/-"]}
PMID:日期:2026-09-01Patients with glutaric acidemia type I (GA I) frequently manifest with acute encephalopathy usually triggered by infections and by progressive neurological deterioration. Since the pathogenesis of the brain damage in GA I during inflammatory processes is poorly established, we investigated biomarkers of inflammatory response and neural damage in the cerebral cortex of wild type (WT) and glutaryl-CoA dehydrogenase (GCDH) deficient mice (Gcdh) receiving acute lysine and lipopolysaccharide (LPS) administration to induce inflammation. Neuromotor development reflexes and the neuroprotective effects of L-carnitine (Carn), whose potent anti-inflammatory properties have been recently described, were also evaluated. LPS increased the gene expression of most parameters of the inflammatory response, which were normalized or attenuated by Carn both in WT and Gcdh mice. Importantly, gene expression of TNF-α, IL-6, NFkB, IκBα, COX-2 and VEGF, and heme oxygenase-1 content were significantly increased in LPS-treated Gcdh relatively to the WT mice. Furthermore, the neuronal biomarker protein NeuN was reduced, whereas the number of vacuoles and neurodegenerative cells were increased in the LPS-treated Gcdh mice, indicating neuronal damage and loss in these animals. Furthermore, the righting and the gait reflexes were altered in the Gcdh mice, reflecting impairment of neuromotor development. Finally, Carn prevented LPS-induced inflammation, neuronal damage, vacuolation, increased neurodegenerative cells and the righting reflex. Our findings suggest that inflammation plays an important role in the pathogenesis of the neurological alterations following infectious/inflammatory processes in GA I patients and that higher doses of Carn should be considered during these episodes.
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4. Longitudinal Assessment of Cognitive Development in 23 Patients With Mucopolysaccharidosis (MPS) Type II: Results of up to 14 Years of Follow-Up.
PMID:日期:2026-09-01This study investigated long-term cognitive development and genotype-phenotype relationships in patients with Mucopolysaccharidosis Type II (MPS II). A nationwide prospective cohort study was conducted in the Netherlands with cognitive follow-up since 2007. Patients were classified as neuronopathic or non-neuronopathic based on iduronate-2-sulphatase (IDS) genotype; novel variants based on age and intelligence quotient (IQ). IQ and Mental Age (MA) were analysed individually and, using linear mixed-effect models, at group level to compare trajectories by genotype and phenotype. Twenty-three male patients (22 children, 1 adult) underwent 136 cognitive assessments, beginning at a median age of 2.9 years with a median follow-up of 6.3 (range 0-13.5) years. IQ and MA trajectories significantly differed between neuronopathic and non-neuronopathic patients (p < 0.001). Non-neuronopathic patients (n = 5) showed normal or mildly impaired cognition. Neuronopathic patients (n = 18) initially developed normally, then stagnated, plateaued, and declined; IQ fell below 70 at a median age of 4 years. Patients with deletions (n = 3) experienced the earliest, most severe impairment (p < 0.001), while those with other IDS variants showed more variable trajectories. Neurocognitive patterns diverge early in MPS II, highlighting the importance of understanding genotype-specific developmental trajectories. This insight is essential for guiding timely brain-targeted interventions, ideally initiated before neurocognitive decline begins.
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5. Distinct Urea Cycle Dysfunction Profiles Differentiate Acute Metabolic Decompensation in TMEM70 and MT-ATP6-Related Mitochondrial ATP Synthase Defects.
PMID:日期:2026-09-01ATP synthase defects, including TMEM70 and MT-ATP6 deficiencies, cause severe mitochondrial encephalo-(cardio)-myopathies complicated by acute metabolic decompensations (AMDs) often associated with hyperammonaemia. However, detailed biochemical characterisation of these events remains limited. The aim of the study was to evaluate the metabolic profiles associated with TMEM70 and MT-ATP6 deficiencies during AMDs in comparison to stable metabolic conditions, assessing frequency and severity of hyperammonaemia, and exploring the mechanisms linking impaired mitochondrial ATP production to the urea cycle by in vivo ureagenesis studies, using [N] ammonium chloride as stable isotope and assessed by high-resolution mass-spectrometry coupled with liquid chromatography. We retrospectively analysed clinical and biochemical profiles from two genetically confirmed cohorts. Patients with TMEM70 deficiency experienced more frequent AMDs, often with hyperammonaemia and requiring extracorporeal detoxification, while the MT-ATP6 cohort had more prominent neurological symptoms and a lower incidence of hyperammonaemia. Biochemically, both groups showed elevated lactate, alanine and glutamine, with orotic aciduria and abnormalities in purine/pyrimidine metabolism. Plasma citrulline levels were divergent in the two cohorts, with a consistent reduction in patients with MT-ATP6 deficiency and normal or borderline elevated levels in the TMEM70 cohort. In vivo stable isotope studies pointed to the differential impact of TMEM70 and MT-ATP6 deficiency on ureagenesis and on the enrichment of individual urea cycle-related amino acids. This study reveals that TMEM70 and MT-ATP6 deficiencies share features of mitochondrial dysfunction but present distinct metabolic profiles, highlighting a different impact on the urea cycle and its related metabolites, and providing novel insights on our understanding of mitochondrial pathophysiology.
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6. Sarcopenia in Pediatric Intoxication Type Inborn Errors of Metabolism: A Frequent and Underrecognized Condition.
PMID:日期:2026-09-01Sarcopenia 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.
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7. Genome Editing for Glycogen Storage Diseases.
PMID:日期:2026-09-01Gene therapy has been developed for several glycogen storage diseases and has advanced into clinical trials. However, the limitations of these gene therapies with regard to stability following treatment early in life have led to the development of genome editing. Early results for genome editing in both glycogen storage disease type Ia and Pompe disease have demonstrated promising efficacy, and proof-of-concept studies as well as a clinical trial are underway. These studies will determine whether genome editing fulfills its promise with regard to stably treating glycogen storage diseases early in life.
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8. Results From a Phase 2, Open-Label Study Evaluating the Safety, Tolerability, and Effect on Ataxia of GLM101 in Three Adult Patients With PMM2-CDG.
PMID:日期:2026-09-01Phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG) is a rare, autosomal recessive disease caused by PMM2 deficiency, which impairs conversion of mannose-6-phosphate into mannose-1-phosphate (M1P) and disrupts N-linked glycosylation. It typically results in a multisystem disorder in which a prominent cerebellar syndrome, characterized by ataxia among other clinical manifestations, can be assessed using the International Cooperative Ataxia Rating Scale (ICARS). GLM101 is a liposomal M1P substrate replacement therapy in clinical development. We present results conducted both within and outside the protocol-defined schedule from three adult patients enrolled in a Phase 2 study evaluating the efficacy, safety, and tolerability of GLM101 (NCT05549219). PMM2-CDG patients received weekly infusions of 30 mg/kg GLM101 for 24 weeks. Ataxia was measured by ICARS as standard of care. Absolute and percent change from baseline were calculated. Additional results reported include global impression of change scales (caregiver and clinician) and safety. Three adult patients (1 M, 2 F) completed 24 weeks of treatment. The mean (SD) baseline ICARS was 50.7 (19.0) and mean (SD) change from baseline was -14.0 (7.2) and -17.7 (3.1) at Weeks 12 and 24, respectively. Improvements were seen across all ICARS subdomains. All patients and clinicians reported global clinical improvement. GLM101 was well tolerated with no serious adverse events. Infusion-associated reactions were reported in one patient, with no need to interrupt the therapy. Safety findings showed no adverse trends. In conclusion, GLM101 was well tolerated and demonstrated potential for meaningful clinical benefit. These findings support continued evaluation of GLM101 in patients with PMM2-CDG.
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9. Mitochondrial CLPP in Health and Disease: Mechanisms, Therapeutic Duality and Emerging Opportunities.
PMID:日期:2026-09-01Mitochondrial CLPP has emerged as an unusual therapeutic target because both increasing and decreasing its proteolytic activity can be beneficial, depending on the cellular and disease context. Pharmacological CLPP hyperactivation drives broad degradation of mitochondrial proteins and can selectively collapse mitochondrial fitness in susceptible tumor cells, an approach now clinically validated by the approval of dordaviprone for mutant diffuse midline glioma. Conversely, reduced CLPP activity can preserve respiratory-chain components and promote adaptive metabolic and redox remodelling in selected models of mitochondrial disease, neurodegeneration and metabolic dysfunction, with emerging potential in ischaemia-reperfusion injury. These opposing outcomes reflect the broader role of CLPXP in controlling mitochondrial translation, respiratory-chain integrity and metabolism rather than acting simply as a general protein quality-control system. In this review, we discuss the physiological functions and substrate selectivity of CLPXP, the mechanistic basis and clinical development of CLPP inhibitors and activators, and the growing evidence that therapeutic responses depend strongly on tissue identity, metabolic state and the nature of the underlying mitochondrial defect. Together, these findings position CLPP as a context-dependent therapeutic switch whose activity may need to be tuned in opposite directions to either preserve mitochondrial resilience or selectively dismantle mitochondrial fitness.
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10. Revisiting Enzyme Replacement Therapy for Aspartylglucosaminuria: Truncated Phosphotransferase Enhances Mannose-6-Phosphorylation and Cellular Uptake of Aspartylglucosaminidase.
PMID:日期:2026-09-01Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by a deficiency of aspartylglucosaminidase (AGA), a hydrolase involved in the degradation of N-glycosylated proteins. Currently, no approved therapies are available for AGU. Development of enzyme replacement therapy (ERT) for AGU has been hampered by the complex proteolytic processing and activation of the AGA enzyme that involves dimerization and cleavage into two subunits. Targeting of AGA into lysosomes is mainly accomplished by a mannose-6-phosphate receptor-mediated pathway, and both AGA subunits contain phosphorylated N-glycans. In this study, we have developed an overexpression system for an optimized human AGA enzyme and a truncated GlcNAc-1-phosphotransferase, S1S3, that is required for the mannose-6-phosphorylation. We here show that the Man-6-phosphorylation and cellular uptake of AGA are enhanced by the coexpression of S1S3, and high amounts of affinity-tagged recombinant human AGA can be expressed in HEK293T cells and purified from the culture medium. Impairment of the N-glycosylation of AGA results in poor uptake into cells, indicating that the Man-6-dependent route is the main endocytic pathway of AGA. Furthermore, for optimal uptake, both subunits of AGA need to be glycosylated and Man-6-phosphorylated. The results of this study enhance the understanding of the lysosomal targeting mechanisms of AGA and pave the way for the development of ERT for AGU.