RARE DISEASE
Glycogen storage disease due to glycogen debranching enzyme deficiency
Glycogen storage disease due to glycogen debranching enzyme deficiency
Glycogen storage disease due to glycogen debranching enzyme deficiency
Synonyms: Amylo-1,6-glucosidase deficiency, Cori disease, Cori-Forbes disease, Forbes disease, GDE deficiency, GSD due to glycogen debranching enzyme deficiency, GSD type 3, GSDIII, Glycogen storage disease type 3, Glycogen storage disease type III, Glycogenosis due to glycogen debranching enzyme deficiency, Glycogenosis type 3, Glycogenosis type III, Limit dextrinosis
Synonyms: Amylo-1,6-glucosidase deficiency, Cori disease, Cori-Forbes disease, Forbes disease, GDE deficiency, GSD due to glycogen debranching enzyme deficiency, GSD type 3, GSDIII, Glycogen storage disease type 3, Glycogen storage disease type III, Glycogenosis due to glycogen debranching enzyme deficiency, Glycogenosis type 3, Glycogenosis type III, Limit dextrinosis
Synonyms: Amylo-1,6-glucosidase deficiency, Cori disease, Cori-Forbes disease, Forbes disease, GDE deficiency, GSD due to glycogen debranching enzyme deficiency, GSD type 3, GSDIII, Glycogen storage disease type 3, Glycogen storage disease type III, Glycogenosis due to glycogen debranching enzyme deficiency, Glycogenosis type 3, Glycogenosis type III, Limit dextrinosis
Drug discovery
2
drugs
With orphan designations
Overview
Glycogen Storage Disease Type III (GSD III) is an autosomal recessive disorder caused by AGL gene mutations, leading to glycogen debranching enzyme deficiency. This results in abnormal glycogen accumulation in the liver, skeletal/cardiac muscles, and occasionally other organs. Clinical features include fasting hypoglycemia, hepatomegaly, hyperlipidemia, and progressive myopathy/cardiomyopathy (GSD IIIa). Variability in phenotype correlates with residual enzyme activity, with liver symptoms often improving by adolescence while neuromuscular complications may progress [1][6][18].
Population
Incidence: ~1:100,000 globally, but higher (~1:5,400) in North African Jewish populations due to founder mutations.
Subtypes: IIIa (85% of cases, liver/muscle involvement), IIIb (15%, liver-limited) [6][14][18].
Age of onset: Symptoms (hypoglycemia, hepatomegaly) typically emerge in infancy/early childhood [1][17].
Burden
Pediatric: Growth retardation, recurrent hypoglycemia, and delayed motor milestones [1][5][16].
Adult: Progressive skeletal myopathy, cardiomyopathy, and cirrhosis in ~20% of cases [1][6][15].
Psychosocial impact: Lifelong dietary restrictions, disability from neuromuscular degeneration, and reduced quality of life [12][15][17].
Therapies
Dietary management: Frequent high-protein meals, uncooked cornstarch to prevent hypoglycemia; may improve growth/metabolic parameters [1][5][15].
Experimental approaches: Truncated GDE gene therapy via AAV vectors (preclinical success in restoring muscle/hepatic function) [3][8][13].
Supportive care: Monitoring for cirrhosis, cardiomyopathy, and myopathy progression [17][18].
Categories: rare cardiac diseases, rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare neurological diseases, rare transplant-related disorders
Research Papers
115 drug discovery papers about Glycogen storage disease due to glycogen debranching enzyme deficiency, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
115 drug discovery papers about Glycogen storage disease due to glycogen debranching enzyme deficiency, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-04-14 | Effects of Extended-Release Cornstarch Supplementation on Glycemic Stability and Metabolic Parameters in Korean Patients with Glycogen Storage Disease.
Background/Objectives: Patients with hepatic glycogen storage disease (GSD) require frequent nighttime intake of uncooked corn starch (UCCS) to prevent fasting hypoglycemia, which imposes a substantial burden. Glycosade, an extended-release cornstarch, was developed to prolong overnight glucose availability. However, data regarding South Korean patients are limited. Therefore, we aimed to evaluate the efficacy and safety of Glycosade in South Korean patients with hepatic GSD. Methods: In this single-center prospective observational study, patients with hepatic GSD underwent laboratory evaluations before and 1 month after Glycosade administration. Continuous glucose monitoring (CGM) was performed during UCCS and Glycosade administration periods. The nocturnal mean glucose, coefficient of variation, time in range (70-180 mg/dL), and time below the range (<70 and <54 mg/dL) were compared between the periods using paired analyses. Results: No significant differences were observed in the nocturnal CGM metrics between the treatment periods. However, time-aligned CGM profiles revealed distinct temporal patterns, with a decline in glucose levels approximately 3-4 h after UCCS intake, whereas Glycosade showed a more sustained glucose profile over an extended period. Liver enzyme and lipid levels improved significantly after 1 month of Glycosade supplementation. Conclusions: In a cohort of South Korean patients with hepatic GSD, Glycosade maintained nocturnal glycemic stability comparable to that of conventional cornstarch without increasing the risk of hypoglycemia. Glycosade was also associated with improved biochemical parameters, supporting its role in nighttime dietary management.
2026-04-02 | Bone mineral density assessment in pediatric patients with hepatic glycogen storage disease subtypes
Background: current scientific literature regarding bone mineral density (BMD) profiles in children with hepatic glycogen storage diseases (GSD) remains sparse. The underlying mechanisms of bone pathology in these patients are not yet fully elucidated. Primary contributors to BMD reduction in GSD include suboptimal metabolic control, mobilization of bone calcium and phosphates to compensate for metabolic shifts, hepatic dysfunction, muscular impairment, hypogonadism, and various micronutrient deficiencies. Aim: to investigate the correlations between BMD parameters and clinical, laboratory, and instrumental findings in pediatric patients with hepatic GSD subtypes. Materials and Methods: the study involved 72 patients aged 4 to 17 years (median age: 8.9 [6.7; 13.8]) diagnosed with GSD types I, III, VI, and IX. Lumbar spine BMD was evaluated using dual-energy X-ray absorptiometry (DXA). Multivariate linear regression was utilized to analyze the associations between variables. Results: the mean BMD Z-score for the entire cohort was within the physiological range (-0.13±1.3). However, 4% (n=3) of patients demonstrated reduced BMD relative to chronological age. A history of at least one fracture was noted in 19% (n=14) of cases, with 5% (n=4) resulting from low-energy trauma. The BMD Z-score showed a significant negative correlation with age (p=0.002) and serum levels of ALT (p=0.031), AST (p=0.028), and alkaline phosphatase (p=0.009). Conversely, positive associations were identified with height Z-score (p<0.001), acid-base status (p=0.02), HDL-cholesterol (p=0.034), glucose levels (p=0.088), and the presence of hepatic fibrosis (p=0.049). Increased fracture incidence was significantly associated with female sex (p=0.039) and liver fibrosis (p=0.02). Conclusion: advanced age, growth retardation (low height Z-score), metabolic disturbances (acidosis, hypoglycemia, dyslipidemia), hepatic cytolysis, and the presence of liver fibrosis represent significant risk factors for BMD reduction in pediatric hepatic GSD KEYWORDS: glycogen storage disease, pediatric patients, bone mineral density, osteoporosis, fractures, liver. FOR CITATION: Rakhmanina K.Yu., Tin I.F., Pavlovskaya E.V., Taran N.N., Bagaeva M.E., Abdulmanapova M.A., Zubovich A.I., Strokova T.V. Bone mineral density assessment in pediatric patients with hepatic glycogen storage disease subtypes. Russian Journal of Woman and Child Health. 2026;9(1):50–60 (in Russ.). DOI: 10.32364/2618-8430-2026-9-1-7
2026-03-09 | Hepatic Glycogen Storage Diseases in Brazil: A Multicenter Study.
To describe clinical and laboratory characteristics, emphasizing the evolution of patients with hepatic glycogen storage diseases (GSDs) followed in Brazilian reference centers. Multicenter, retrospective study involving 13 centers, using RedCap platform. 132 patients were included: 63 (47.8%) GSD type I (56 Ia, 7 Ib), 13 (9.8%) with type III (12 IIIa, 1 IIIb), 1 (0.8%) type IV, 6 (4.5%) type VI, and 49 (37.1%) with type IX (28 IXa, 7 IXb, and 14 IXc). Type I patients presented earlier (4 months) and had more episodes of hypoglycemia at clinical presentation (p < 0.001). Anthropometric data at admission revealed impaired growth, with a tendency toward short stature across the groups (median -2.06, -1.89, and -1.96 among type I, III, and IX respectively). The median body mass index (BMI) z-scores at admission for all three types were above +1. Only patients with type IX demonstrated significant improvement in height (p = 0.007) and BMI (p = 0.020) z-scores during follow-up. Regarding laboratory tests, significant decreases were observed in total cholesterol, triglycerides, venous lactate and aminotransferases in patients with types I and IX. Hepatic GSDs are heterogeneous diseases. There is a significant height impairment with a troublesome trend to overweight and obesity, especially in type I. Although there is improvement in aminotransferases, cholesterol, and triglycerides with follow-up, adherence to treatment remains a challenge.
2026-04-14 | Effects of Extended-Release Cornstarch Supplementation on Glycemic Stability and Metabolic Parameters in Korean Patients with Glycogen Storage Disease.
Background/Objectives: Patients with hepatic glycogen storage disease (GSD) require frequent nighttime intake of uncooked corn starch (UCCS) to prevent fasting hypoglycemia, which imposes a substantial burden. Glycosade, an extended-release cornstarch, was developed to prolong overnight glucose availability. However, data regarding South Korean patients are limited. Therefore, we aimed to evaluate the efficacy and safety of Glycosade in South Korean patients with hepatic GSD. Methods: In this single-center prospective observational study, patients with hepatic GSD underwent laboratory evaluations before and 1 month after Glycosade administration. Continuous glucose monitoring (CGM) was performed during UCCS and Glycosade administration periods. The nocturnal mean glucose, coefficient of variation, time in range (70-180 mg/dL), and time below the range (<70 and <54 mg/dL) were compared between the periods using paired analyses. Results: No significant differences were observed in the nocturnal CGM metrics between the treatment periods. However, time-aligned CGM profiles revealed distinct temporal patterns, with a decline in glucose levels approximately 3-4 h after UCCS intake, whereas Glycosade showed a more sustained glucose profile over an extended period. Liver enzyme and lipid levels improved significantly after 1 month of Glycosade supplementation. Conclusions: In a cohort of South Korean patients with hepatic GSD, Glycosade maintained nocturnal glycemic stability comparable to that of conventional cornstarch without increasing the risk of hypoglycemia. Glycosade was also associated with improved biochemical parameters, supporting its role in nighttime dietary management.
2026-04-02 | Bone mineral density assessment in pediatric patients with hepatic glycogen storage disease subtypes
Background: current scientific literature regarding bone mineral density (BMD) profiles in children with hepatic glycogen storage diseases (GSD) remains sparse. The underlying mechanisms of bone pathology in these patients are not yet fully elucidated. Primary contributors to BMD reduction in GSD include suboptimal metabolic control, mobilization of bone calcium and phosphates to compensate for metabolic shifts, hepatic dysfunction, muscular impairment, hypogonadism, and various micronutrient deficiencies. Aim: to investigate the correlations between BMD parameters and clinical, laboratory, and instrumental findings in pediatric patients with hepatic GSD subtypes. Materials and Methods: the study involved 72 patients aged 4 to 17 years (median age: 8.9 [6.7; 13.8]) diagnosed with GSD types I, III, VI, and IX. Lumbar spine BMD was evaluated using dual-energy X-ray absorptiometry (DXA). Multivariate linear regression was utilized to analyze the associations between variables. Results: the mean BMD Z-score for the entire cohort was within the physiological range (-0.13±1.3). However, 4% (n=3) of patients demonstrated reduced BMD relative to chronological age. A history of at least one fracture was noted in 19% (n=14) of cases, with 5% (n=4) resulting from low-energy trauma. The BMD Z-score showed a significant negative correlation with age (p=0.002) and serum levels of ALT (p=0.031), AST (p=0.028), and alkaline phosphatase (p=0.009). Conversely, positive associations were identified with height Z-score (p<0.001), acid-base status (p=0.02), HDL-cholesterol (p=0.034), glucose levels (p=0.088), and the presence of hepatic fibrosis (p=0.049). Increased fracture incidence was significantly associated with female sex (p=0.039) and liver fibrosis (p=0.02). Conclusion: advanced age, growth retardation (low height Z-score), metabolic disturbances (acidosis, hypoglycemia, dyslipidemia), hepatic cytolysis, and the presence of liver fibrosis represent significant risk factors for BMD reduction in pediatric hepatic GSD KEYWORDS: glycogen storage disease, pediatric patients, bone mineral density, osteoporosis, fractures, liver. FOR CITATION: Rakhmanina K.Yu., Tin I.F., Pavlovskaya E.V., Taran N.N., Bagaeva M.E., Abdulmanapova M.A., Zubovich A.I., Strokova T.V. Bone mineral density assessment in pediatric patients with hepatic glycogen storage disease subtypes. Russian Journal of Woman and Child Health. 2026;9(1):50–60 (in Russ.). DOI: 10.32364/2618-8430-2026-9-1-7
2026-03-09 | Hepatic Glycogen Storage Diseases in Brazil: A Multicenter Study.
To describe clinical and laboratory characteristics, emphasizing the evolution of patients with hepatic glycogen storage diseases (GSDs) followed in Brazilian reference centers. Multicenter, retrospective study involving 13 centers, using RedCap platform. 132 patients were included: 63 (47.8%) GSD type I (56 Ia, 7 Ib), 13 (9.8%) with type III (12 IIIa, 1 IIIb), 1 (0.8%) type IV, 6 (4.5%) type VI, and 49 (37.1%) with type IX (28 IXa, 7 IXb, and 14 IXc). Type I patients presented earlier (4 months) and had more episodes of hypoglycemia at clinical presentation (p < 0.001). Anthropometric data at admission revealed impaired growth, with a tendency toward short stature across the groups (median -2.06, -1.89, and -1.96 among type I, III, and IX respectively). The median body mass index (BMI) z-scores at admission for all three types were above +1. Only patients with type IX demonstrated significant improvement in height (p = 0.007) and BMI (p = 0.020) z-scores during follow-up. Regarding laboratory tests, significant decreases were observed in total cholesterol, triglycerides, venous lactate and aminotransferases in patients with types I and IX. Hepatic GSDs are heterogeneous diseases. There is a significant height impairment with a troublesome trend to overweight and obesity, especially in type I. Although there is improvement in aminotransferases, cholesterol, and triglycerides with follow-up, adherence to treatment remains a challenge.
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Drug Discovery Landscape
2 orphan drug designations for Glycogen storage disease due to glycogen debranching enzyme deficiency.
2 orphan drug designations for Glycogen storage disease due to glycogen debranching enzyme deficiency.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
mRNA encoding the human glycogen debranching enzyme | gene therapies | EMA | 2021-07-19 | — | Ultragenyx Germany GmbH |
mRNA encoding the human glycogen debranching enzyme | RNAs | FDA | 2021-06-24 | — | Ultragenyx Pharmaceutical Inc. |
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