Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly

Quackenbush, David; Devito, Justin; Garibaldi, Luigi; Buryk, Melissa

doi:10.1515/jpem-2017-0209

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…Several case reports and large cohort studies were reported for GSD III, [20][21][22][23][24][25][26] summarized in Table S1. Large cohorts included patients with ages averaging 26 years, 10 19 years, 12 or 17 years.…”

Section: Review Of Literature For Gsd III Patientsmentioning

confidence: 99%

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring

Halaby

Young

Austin

et al. 2019

Genetics in Medicine

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In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age. Methods: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings. Results: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc 4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4). Conclusion: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc 4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.

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Section: Review Of Literature For Gsd III Patientsmentioning

confidence: 99%

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring

Halaby

Young

Austin

et al. 2019

Genetics in Medicine

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“…The pathophysiology of these endocrine manifestations is not yet well understood, but insulin resistance (due to regular ingestion of glucose and excess body weight) appears to be one of the main factors [ 50 , 51 ].…”

Section: Diagnosis and Initial Assessmentmentioning

confidence: 99%

French recommendations for the management of glycogen storage disease type III

Wicker¹,

Cano²,

Decostre³

et al. 2023

Eur J Med Res

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The aim of the Protocole National De Diagnostic et de Soins/French National Protocol for Diagnosis and Healthcare (PNDS) is to provide advice for health professionals on the optimum care provision and pathway for patients with glycogen storage disease type III (GSD III).The protocol aims at providing tools that make the diagnosis, defining the severity and different damages of the disease by detailing tests and explorations required for monitoring and diagnosis, better understanding the different aspects of the treatment, defining the modalities and organisation of the monitoring. This is a practical tool, to which health care professionals can refer. PNDS cannot, however, predict all specific cases, comorbidities, therapeutic particularities or hospital care protocols, and does not seek to serve as a substitute for the individual responsibility of the physician in front of his/her patient.

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“…It is relatively rare with an estimated incidence of 1 : 100000 births [2]. GSDIII is a subtype of hepatic glycogen storage disease (GSDs), presenting with hepatomegaly, hepatic dysfunction, hypoglycemia, hyperlipidemia, growth retardation, as well as progressive myopathy and cardiomyopathy [3][4][5][6][7][8]. Tere are four subtypes in GSDIII classifed based on the diference of the tissues involved and variated regions of the GSD enzyme.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Functional Characterization of Novel AGL Variants in Two Families with Glycogen Storage Disease Type III

Yang

et al. 2023

International Journal of Endocrinology

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Purpose. Glycogen storage disease type III (GSDIII) is a uncommon autosomal recessive inherited metabolic disorder, which is caused by variants in the AGL gene. The purpose of this study was to elucidate the clinical and functional features of two novel variants in two families with GSDIIIa. Methods. We collected the clinical and laboratory data of the two patients. Genetic testing was performed using GSDs gene panel sequencing, and the identified variants were classified according to the American College of Medical Genetics (ACMG) criteria. The pathogenicity of the novel variants was furthermore assessed through bioinformatics analysis and cellular functional validation experiments. Results. The two patients were hospitalized with abnormal liver function or hepatomegaly, which was characterized by remarkably elevated liver enzyme and muscle enzyme levels, as well as hepatomegaly, and were eventually diagnosed with GSDIIIa. Genetic analysis detected two novel variants of AGL gene in the two patients: c.1484A > G (p.Y495C), c.1981G > T (p.D661Y). Bioinformatics analysis indicated that the two novel missense mutations most likely altered the protein’s conformation and therefore made the enzyme it encodes less active. Based on the ACMG criteria, both variants were considered likely pathogenic, in accordance with the functional analysis results, which demonstrated that the mutated protein was still localized in the cytoplasm and that the glycogen content of cells transfected with the mutated AGL was increased compared to cells transfected with the wild-type one. Conclusion. These findings indicated that the two newly identified variants in the AGL gene (c.1484A > G; c.1981G > T) were undoubtedly pathogenic mutations, inducing a slight reduction in glycogen debranching enzyme activity and a mild increase in intracellular glycogen content. Two patients who visited us with abnormal liver function, or hepatomegaly, improved dramatically after treatment with oral uncooked cornstarch, but the effects on skeletal muscle and myocardium required further observation.

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Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly

Abstract: They highlight the importance of considering glycogen storage disease in a child presenting with short stature, as it is a treatable disease that can be diagnosed non-invasively with genetic testing.

Cited by 5 publications

References 8 publications

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring

French recommendations for the management of glycogen storage disease type III

Clinical and Functional Characterization of Novel AGL Variants in Two Families with Glycogen Storage Disease Type III

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