<i>In Utero</i>Stem Cell Transplantation, Enzyme Replacement, and Gene Therapy

MacKenzie, Tippi C.; Schwab, Marisa E.

doi:10.1002/9781119676980.ch30

Cited by 1 publication

(1 citation statement)

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“…Classic IOPD results from the complete or near-complete deficiency of GAA activity. This phenotype is clinically characterized by the onset of symptoms soon after birth [ 30 ], sometimes even manifesting prenatally [ 31 , 32 ], and requires early treatment for best outcomes [ 33 , 34 , 35 , 36 ]. In contrast, LOPD is characterized by later onset of symptoms, with a high heterogeneity in clinical presentation, usually characterized by muscle weakness with a limb girdle pattern, that leads to progressive respiratory insufficiency [ 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Omics-Based Approaches for the Characterization of Pompe Disease Metabolic Phenotypes

Gómez-Cebrián,

Gras-Colomer,

Poveda Andrés

et al. 2023

Biology

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Lysosomal storage disorders (LSDs) constitute a large group of rare, multisystemic, inherited disorders of metabolism, characterized by defects in lysosomal enzymes, accessory proteins, membrane transporters or trafficking proteins. Pompe disease (PD) is produced by mutations in the acid alpha-glucosidase (GAA) lysosomal enzyme. This enzymatic deficiency leads to the aberrant accumulation of glycogen in the lysosome. The onset of symptoms, including a variety of neurological and multiple-organ pathologies, can range from birth to adulthood, and disease severity can vary between individuals. Although very significant advances related to the development of new treatments, and also to the improvement of newborn screening programs and tools for a more accurate diagnosis and follow-up of patients, have occurred over recent years, there exists an unmet need for further understanding the molecular mechanisms underlying the progression of the disease. Also, the reason why currently available treatments lose effectiveness over time in some patients is not completely understood. In this scenario, characterization of the metabolic phenotype is a valuable approach to gain insights into the global impact of lysosomal dysfunction, and its potential correlation with clinical progression and response to therapies. These approaches represent a discovery tool for investigating disease-induced modifications in the complete metabolic profile, including large numbers of metabolites that are simultaneously analyzed, enabling the identification of novel potential biomarkers associated with these conditions. This review aims to highlight the most relevant findings of recently published omics-based studies with a particular focus on describing the clinical potential of the specific metabolic phenotypes associated to different subgroups of PD patients.

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