Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature

Paschall, Anna K.; Khan, Aleena; Enam, Syed Faaiz; Boggs, Tracy; Hijazi, Ghada; Bowling, Michael; Austin, Stephanie; Case, Laura E.; Kishnani, Priya S.

doi:10.1016/j.ymgme.2021.10.002

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…A retrospective, longitudinal natural history study detailed the clinical, biochemical, radiological, functional, and histopathological aspects of the disease course in adults with GSD III ( N = 25) as well as confirmed the use of Glc 4 as a biomarker of GSD III 110 . Furthermore, the musculoskeletal manifestations in GSD IIIa from affected pediatric and adult individuals ( N = 22) were detailed, providing support for monitoring performance on functional assessments in future clinical trials 111 …”

Section: Natural History and Animal Models For The Gsdsmentioning

confidence: 80%

“…110 Furthermore, the musculoskeletal manifestations in GSD IIIa from affected pediatric and adult individuals (N = 22) were detailed, providing support for monitoring performance on functional assessments in future clinical trials. 111 Four GSD III mouse models with different Agl gene variants have been described, all demonstrating glycogen accumulation in the muscle and liver (Table 2). [32][33][34][35] There is also a naturally occurring curly-coated retriever dog model that demonstrates initial elevations of liver enzymes, muscle enzymes, and urine Glc 4 , as well as hepatomegaly with glycogen accumulation in liver and muscle.…”

Section: Gsd IIImentioning

confidence: 99%

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Gene therapy for glycogen storage diseases

Koeberl

Koch

Lim

et al. 2023

J of Inher Metab Disea

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Glycogen storage disorders (GSDs) are inherited disorders of metabolism resulting from the deficiency of individual enzymes involved in the synthesis, transport, and degradation of glycogen. This literature review summarizes the development of gene therapy for the GSDs. The abnormal accumulation of glycogen and deficiency of glucose production in GSDs lead to unique symptoms based upon the enzyme step and tissues involved, such as liver and kidney involvement associated with severe hypoglycemia during fasting and the risk of long‐term complications including hepatic adenoma/carcinoma and end stage kidney disease in GSD Ia from glucose‐6‐phosphatase deficiency, and cardiac/skeletal/smooth muscle involvement associated with myopathy +/− cardiomyopathy and the risk for cardiorespiratory failure in Pompe disease. These symptoms are present to a variable degree in animal models for the GSDs, which have been utilized to evaluate new therapies including gene therapy and genome editing. Gene therapy for Pompe disease and GSD Ia has progressed to Phase I and Phase III clinical trials, respectively, and are evaluating the safety and bioactivity of adeno‐associated virus vectors. Clinical research to understand the natural history and progression of the GSDs provides invaluable outcome measures that serve as endpoints to evaluate benefits in clinical trials. While promising, gene therapy and genome editing face challenges with regard to clinical implementation, including immune responses and toxicities that have been revealed during clinical trials of gene therapy that are underway. Gene therapy for the glycogen storage diseases is under development, addressing an unmet need for specific, stable therapy for these conditions.

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Section: Natural History and Animal Models For The Gsdsmentioning

confidence: 80%

Section: Gsd IIImentioning

confidence: 99%

Gene therapy for glycogen storage diseases

Koeberl

Koch

Lim

et al. 2023

J of Inher Metab Disea

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“…The nature of GSD IIIa myopathy appears to progress with age with onset increasingly reported in childhood [45] . Generalized muscle weakness was the most common form of myopathy found in our cohort and observed in a majority of patients.…”

Section: Discussionmentioning

confidence: 99%

A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III

Hijazi

Paschall

Young

et al. 2021

Molecular Genetics and Metabolism Reports

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“…Two subtests on the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) were utilized: running speed and agility (subtest 6) and strength (subtest 8) (Deitz et al, 2007). For the patient who was non-ambulatory, the 9-Hole Peg Test (9-HPT) was used to measure hand dexterity (Wang et al, 2015), and lateral (key) pinch was used to assess strength as previously described (Paschall et al, 2021).…”

Section: Physical Therapy Outcome Measuresmentioning

confidence: 99%

Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa

Carter,

Boggs,

Case

et al. 2024

Front. Genet.

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Introduction: Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues. There have been trials comparing the efficacy of alglucosidase and avalglucosidase, but there remains a need for more real-world data on patients who switched from alglucosidase to avalglucosidase.Methods: A chart review was conducted on n = 15 patients with late-onset Pompe disease followed at a single center who switched from alglucosidase to avalglucosidase and continued for at least 6 months.Results: A total of n = 8/15 patients received alglucosidase for more than 3 years prior to switching, and n = 7/15 received it for more than 5 years prior to switching. There were statistically significant improvements in CK, Hex4, and AST with mean differences of −104.8 U/L, −3.0 mmol/molCr, and −14.7 U/L, respectively, post-switch. 6-Minute Walk Test; comfortable gait speed; Gait, Stairs, Gower, Chair; and Quick Motor Function Test scores improved or stabilized in most patients post-switch (n = 8/12, n = 11/12, n = 9/12, n =7/11, respectively). Of n = 7 patients with pulmonary function testing, n = 4/7 had improved upright FVC. Patient-reported outcomes revealed improvements in dyspnea (n = 4/4), physical function (n = 3/4), fatigue (n = 2/3), and lower back pain (n = 3/3). Avalglucosidase was well tolerated without infusion-associated reactions, and all n = 7 patients on home infusions continued receiving ERT at home. Anti-drug antibodies were seen in n = 9/10 of patients on alglucosidase and n = 8/13 of those on avalglucosidase, with titers below 12,800 in a majority of patients. We also present the first outcome data for a patient with LOPD who is non-ambulatory and a full-time wheelchair user; she demonstrated meaningful improvements in quality of life and motor function with the switch.Discussion: In summary, improved outcomes were seen in most patients, with a subset whose decline persisted. This study presents evidence that switching from alglucosidase to avalglucosidase may be associated with improved outcomes in certain patients with LOPD.

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Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature

Cited by 4 publications

References 30 publications

Gene therapy for glycogen storage diseases

Gene therapy for glycogen storage diseases

A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III

Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa

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