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http://dx.doi.org/10.1016/j.amjmed.2020.11.020 | DOI Listing |
Pediatr Neurol
August 2025
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina. Electronic address:
Pompe disease (PD), an autosomal recessive lysosomal disorder, results in glycogen accumulation in muscle cells, leading to progressive muscle weakness and respiratory insufficiency. Newborn screening (NBS) has improved outcomes for infantile-onset PD by enabling early diagnosis and intervention with enzyme replacement therapy. NBS also identifies late-onset PD (LOPD) cases, wherein children have a wide clinical spectrum and may remain asymptomatic for years, placing families in uncertainty as "patients-in-waiting.
View Article and Find Full Text PDFClin Chim Acta
August 2025
Laboratorio Chamoles, Uriarte 2383, C1425FNH Ciudad Autónoma de Buenos Aires, Argentina; Sanofi Argentina, Cuyo 3532, B1640GJC Martínez, Provincia de Buenos Aires, Argentina.
Introduction: The gold standard for diagnosing Gaucher disease (GD) is the detection of reduced beta-glucosidase (bGlu) activity in peripheral blood samples, in association with variant analysis of the GBA1 gene. Dried blood spot (DBS) specimens are accepted worldwide for first-tier testing of GD. Glucosylsphingosine (Lyso-Gb1) is considered an ideal disease biomarker.
View Article and Find Full Text PDFGaucher disease type 1 is a lysosomal storage disorder caused by mutations that reduce glucocerebrosidase activity, leading to glycolipid buildup, particularly in macrophages. To develop a curative approach, we established a high-efficiency genome editing platform for human and murine hematopoietic stem-progenitor cells using CRISPR/Cas9, recombinant adeno-associated virus serotype 6. To enhance homology-directed DNA repair while minimizing genotoxicity, we incorporated a new 53BP1 inhibitor, a ubiquitin variant that promotes DNA end resection and significantly increases editing efficiency.
View Article and Find Full Text PDFBiochemistry (Mosc)
August 2025
Institute of Molecular Genetics, Kurchatov Institute National Research Centre, Moscow, 123182, Russia.
The deficiency of glucocerebrosidase (GCase) encoded by the gene, leads to the autosomal recessive Gaucher disease and highly increased risk of developing Parkinson's disease (PD). In order to study the effect of GCase dysfunction on neurodegeneration, we evaluated the GCase activity, lysosphingolipid content, extent of dopaminergic neuron degeneration in the substantia nigra (SN), and levels of dopamine (DA) and total and oligomeric α-synuclein (α-Syn) in the brain of mice with the presymptomatic stage of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in combination with a single injection of the GCase selective inhibitor conduritol-β-epoxide (CBE) (100 mg/kg body weight). A single injection of CBE led to a ~50% decrease in the GCase activity, significant increase in the lysosphingolipid content, and striatal accumulation of oligomeric α-Syn in the mouse brain.
View Article and Find Full Text PDFNeurobiol Dis
August 2025
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:
GBA variants are among the most significant genetic risk factors for synucleinopathies including Parkinson's disease and dementia with Lewy bodies. The GBA gene encodes the lysosomal enzyme glucocerebrosidase (GBA), which is essential for glycosphingolipid catabolism. There is a reciprocal relationship between GBA and α-synuclein (α-syn), in which reduced GBA levels lead to elevated α-syn.
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