Showing papers in "Molecular Genetics and Metabolism in 2020"

TL;DR: There is a critical unmet need for safe and effective disease-modifying therapies for MSUD which can be implemented early in life and key insights into the design of new therapies based on gene replacement or editing are afforded.

TL;DR: The direct and indirect effects of Coronavirus Disease-19 pandemic, on Italian patients with lysosomal storage disorders receiving therapy, were analyzed by a phone questionnaire and no proved COVID-19 emerged among 102 interviewed.

TL;DR: Preliminary data support further development of rhASA as a therapy for patients with MLD, with a tendency towards a less pronounced decline in motor function in patients receiving 100 mg EOW.

TL;DR: This review will cover different treatment modalities currently used in mitochondrial disorders, focusing on recent and ongoing clinical trials.

TL;DR: The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60–80% with a profound impact on patient management and care for this vulnerable patient group.

TL;DR: In patients with Fabry disease and amenable GLA variants, migalastat 150 mg QOD was well tolerated and demonstrated durable, long-term stability of renal function and reduction in LVMi.

TL;DR: The lysine degradation pathway is clinically relevant due to the occurrence of two severe neurometabolic disorders, pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1) and the possibility to find alternative therapeutic strategies for PDE and GA1 through pathway modulation is opened up.

TL;DR: In this article, the authors analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse glutaric acidemia type 1 (GA1) patients managed at a single center over 31 years.

TL;DR: The findings are consistent with mTOR inhibition alleviating disease by increasing availability of α-ketoglutarate, which is both an efficient mitochondrial complex I substrate in Ndufs4(KO) and an important metabolite related to neurotransmitter metabolism in glutamatergic neurons.

TL;DR: A founder effect of FD due to the p.F113L mutation was demonstrated in a large cohort of genetically related adult patients, living in the same region of Guimarães, suggesting a founder effect that was supported by haplotype findings.

TL;DR: This report describes the methodology used in the development of the nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency including review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; expert input through two Delphi surveys and a nominal group process.

TL;DR: Plasma lyso-Gb3 has high sensitivity and specificity for Fabry disease in males and females, and provides supportive diagnostic information when gene sequencing results are negative or inconclusive, and reflexing to gene sequencing and plasma lyso -Gb3 is useful for disease confirmation in males.

TL;DR: The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments, and emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

TL;DR: Results show for the first time that TGF-β1 is expressed in human renal tissue from Fabry patients, and that this profibrotic cytokine is mainly produced by proximal tubular cells.

TL;DR: Results demonstrate that plasma PPCS was able to diagnose NPC1 patients with high sensitivity and specificity, and to evaluate the peripheral treatment efficacy of IV HPβCD treatment.

TL;DR: In this review, notable metabolic studies of the last decade are discussed and their application to novel therapies are discussed.

TL;DR: The data show that GlcSph but not SapC is the antigenic target in GD1-associated MG and that therapy aimed at reducing the levels of immunogenic lipid resulted in reduction of clonal immunoglobulin in vivo.

TL;DR: L Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

TL;DR: The goals of the UDNI are to provide diagnoses for individuals who have conditions that have eluded diagnosis by clinical experts, gain insights into the etiology and pathogenesis of novel diseases, and contribute to standards of diagnosing unsolved patients.

TL;DR: This article expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses.

TL;DR: Newborn screening provides the opportunity to reduce morbidity and post-neonatal mortality in all patients with MCAD deficiency, regardless of genotype, as well as compare biochemical data with clinical outcomes.

TL;DR: High levels of propionate resulted in high levels of intracellular P-CoA in normal hepatocytes, and it was found that the isoleucine and valine catabolism pathways are the greatest sources of P- coA in PA and MMA donor cells.

TL;DR: This review covers various qualitative and quantitative methods for measurement of GAGs, including dye specific, thin layer chromatography (TLC), capillary electrophoresis, high-performance liquid Chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography, ELISA, and automated high-throughput mass Spectrometry.

TL;DR: Several plasma markers of lipid-laden cells, fibrosis or inflammation are of high potential as biomarkers and deserve further study and are suggested as the most promising biomarkers that may function as surrogate endpoints in the future.

TL;DR: Clinical, biochemical and molecular analysis of five patients with sialidosis type I and the impact of these new mutations on the structural properties of NEU1 are discussed, with the aim of identifying the most frequent initial clinical manifestations and achieving more focused diagnoses.

TL;DR: The generation of a novel, highly sialylated version of recombinant human β-glucuronidase (rhGUS), vestronidase alfa, that has high uptake is presented, resulting in an improved enzyme replacement therapy for the treatment of patients with MPS VII.

TL;DR: In this paper, the authors conducted a retrospective study to evaluate prognosis among at-risk female family members depending on the primary method of diagnosis, including mutation analysis and biochemical analysis.

TL;DR: The results show that a non-invasive, bigenomic sequencing (BGS) approach (using both a nWES and optimized mtDNA analysis to include large deletions) should be the first step in investigating for mitochondrial diseases.

TL;DR: The comprehensive review demonstrates quantitatively that the clinical presentation of GSD IX γ2 patients is more severe than that of G SD IX α2 or β patients, and shows the existence of a severe phenotype in GSD VIII α2, evidenced by early onset liver pathology in conjunction with clinical symptoms.