A novel approach to characterize phenotypic variation in GSD IV: Reconceptualizing the clinical continuum

Kiely, Bridget T.; Koch, Rebecca L.; Flores, Leticia; Burner, Danielle; Kaplan, Samantha; Kishnani, Priya S.

doi:10.3389/fgene.2022.992406

Cited by 8 publications

(13 citation statements)

References 29 publications

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“…2 Additionally, a recent review of all published cases with GSD IV that had symptom onset before the age of 25 years (N = 179) evaluated the extent of multisystem tissue involvement and revealed the pitfalls of the traditional subtype classification system. 113 Rather than classifying patients into discrete hepatic or neuromuscular subtypes, Kiely et al 113 recognized that GBE deficiency can cause a spectrum of manifestations across multiple tissue systems and affected individuals may exhibit differing degrees of hepatic, neuromuscular, and/or cardiac involvement over time. An additional natural history study focused on APBD (N = 50 cases) defined the cardinal signs of the disease and the typical stages of disease progression.…”

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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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: 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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“…Historically, six clinical subtypes of GSD IV were distinguished, depending on the clinical presentation (hepatic, neuromuscular, or both), the age of onset and the severity. 3,4 In particular, severe neuromuscular presentations were either classified as the fatal perinatal subtype, with hydrops fetalis, joint contractures, and perinatal death or as the congenital/ neonatal subtype, presenting at birth with severe hypotonia, muscle atrophy, with the need for mechanical ventilation and death in the neonatal period or in early infancy. The use of this subtype system was flawed given the degree of phenotypic heterogeneity of this disease, the overlap in clinical features and the lack of clear prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…Kiely and colleagues recently proposed a more accurate conceptualization of GSD IV as a multidimensional clinical continuum, based on a phenotypic characterization score scaling the neuromuscular, hepatic, and cardiac involvement. 3 Following this novel approach, we present clinical, histological, biochemical, and molecular findings of 10 unpublished cases of severe neuromuscular GSD IV diagnosed in our laboratory (Biochemistry and Molecular Biology Department, Lyon, France). Three other cases from our laboratory that have been previously published are not included in this series (one case referred to as 'congenital case' 5 ) and two cases referred to as 'perinatal cases' 6,7 ).…”

Section: Introductionmentioning

confidence: 99%

“…GSD IV is a phenotypic continuum with a broad heterogeneity in the age of onset, the clinical spectrum, the severity of the affected tissues, making the diagnosis difficult to establish. Historically, six clinical subtypes of GSD IV were distinguished, depending on the clinical presentation (hepatic, neuromuscular, or both), the age of onset and the severity 3,4 . In particular, severe neuromuscular presentations were either classified as the fatal perinatal subtype, with hydrops fetalis, joint contractures, and perinatal death or as the congenital/neonatal subtype, presenting at birth with severe hypotonia, muscle atrophy, with the need for mechanical ventilation and death in the neonatal period or in early infancy.…”

Section: Introductionmentioning

confidence: 99%

“…The use of this subtype system was flawed given the degree of phenotypic heterogeneity of this disease, the overlap in clinical features and the lack of clear prognosis. Kiely and colleagues recently proposed a more accurate conceptualization of GSD IV as a multidimensional clinical continuum, based on a phenotypic characterization score scaling the neuromuscular, hepatic, and cardiac involvement 3 . Following this novel approach, we present clinical, histological, biochemical, and molecular findings of 10 unpublished cases of severe neuromuscular GSD IV diagnosed in our laboratory (Biochemistry and Molecular Biology Department, Lyon, France).…”

Section: Introductionmentioning

confidence: 99%

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Severe neuromuscular forms of glycogen storage disease type IV: Histological, clinical, biochemical, and molecular findings in a large French case series

Lefèvre,

Collardeau‐Frachon,

Streichenberger

et al. 2023

J of Inher Metab Disea

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Glycogen storage disease type IV (GSD IV), also called Andersen disease, or amylopectinosis, is a highly heterogeneous autosomal recessive disorder caused by a glycogen branching enzyme (GBE, 1,4‐alpha‐glucan branching enzyme) deficiency secondary to pathogenic variants on GBE1 gene. The incidence is evaluated to 1:600 000 to 1:800 000 of live births. GBE deficiency leads to an excessive deposition of structurally abnormal, amylopectin‐like glycogen in affected tissues (liver, skeletal muscle, heart, nervous system, etc.). Diagnosis is often guided by histological findings and confirmed by GBE activity deficiency and molecular studies. Severe neuromuscular forms of GSD IV are very rare and of disastrous prognosis. Identification and characterization of these forms are important for genetic counseling for further pregnancies. Here we describe clinical, histological, enzymatic, and molecular findings of 10 cases from 8 families, the largest case series reported so far, of severe neuromuscular forms of GSD IV along with a literature review. Main antenatal features are: fetal akinesia deformation sequence or arthrogryposis/joint contractures often associated with muscle atrophy, decreased fetal movement, cystic hygroma, and/or hydrops fetalis. If pregnancy is carried to term, the main clinical features observed at birth are severe hypotonia and/or muscle atrophy, with the need for mechanical ventilation, cardiomyopathy, retrognathism, and arthrogryposis. All our patients were stillborn or died within 1 month of life. In addition, we identified five novel GBE1 variants.

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