Cornstarch Therapy in Type I Glycogen-Storage Disease

Chen, Yuan-Tsong; Cornblath, Marvin; Sidbury, James

doi:10.1056/nejm198401193100306

Cited by 294 publications

(155 citation statements)

References 9 publications

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“…GSD-Ib patients exhibit additional clinical manifestations of neutropenia and myeloid dysfunctions (1)(2)(3)(4). In the last two and half decades, effective dietary therapies (5,6) have significantly alleviated the metabolic abnormalities of GSD-I. However, hepatocellular adenoma (HCA) with risk for spontaneous hemorrhage and malignant transformation remains a long-term presentation of unknown etiology (7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

Kim

Weinstein

Starost

et al. 2008

Journal of Hepatology

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Background/Aims-Glycogen storage disease type Ia (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver.Methods-Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice.Results-We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines.Conclusion-Peripheral neutrophilia and elevated serum chemokines are characteristic of GSDIa with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia

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Section: Introductionmentioning

confidence: 99%

Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

Kim

Weinstein

Starost

et al. 2008

Journal of Hepatology

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“…1,2 Over the last 25 years, dietary therapy consisting of nocturnal nasogastric infusion of glucose 3 or frequent oral administration of uncooked cornstarch 4 has significantly alleviated the metabolic abnormalities of GSD-Ia and greatly improved the prognosis. However, the underlying disease remains untreated and patients continue to suffer from hyperlipidemia, hyperuricemia, hypercalciuria, hypocitraturia, and lactic acidemia.…”

Section: Introductionmentioning

confidence: 99%

Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer

Ghosh

et al. 2005

Gene Ther

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Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-a (G6Pase-a), a ninetransmembrane domain, endoplasmic reticulum-associated protein expressed primarily in the liver and kidney. Previously, we showed that infusion of an adeno-associated virus (AAV) serotype 2 vector carrying murine G6Pase-a (AAV2-G6Pase-a) into neonatal GSD-Ia mice failed to sustain their life beyond weaning. We now show that neonatal infusion of GSD-Ia mice with an AAV serotype 1-G6Pase-a (AAV1-G6Pase-a) or AAV serotype 8-G6Pase-a (AAV8-G6Pase-a) results in hepatic expression of the G6Pase-a transgene and markedly improves the survival of the mice. However, only AAV1-G6Pase-a can achieve significant renal transgene expression. A more effective strategy, in which a neonatal AAV1-G6Pase-a infusion is followed by a second infusion at age 1 week, provides sustained expression of a complete, functional, G6Pase-a system in both the liver and kidney and corrects the metabolic abnormalities in GSD-Ia mice for the 57 week length of the study. This effective use of gene therapy to correct metabolic imbalances and disease progression in GSD-Ia mice holds promise for the future of gene therapy in humans. Gene Therapy (2005) 13, 321-329.

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“…In the early 1980s, uncooked cornstarch was introduced as a treatment for maintaining normoglycemia (Chen et al 1984), and it has remained the mainstay of therapy in North America (Koeberl et al 2007). While cornstarch has dramatically improved the quality of life and clinical outcome for patients with GSD I, it has a limited duration of action.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Chronic Extended Release Cornstarch Therapy for Glycogen Storage Disease Type I

et al. 2015

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Background: Glycogen storage disease type I (GSD I) causes severe hypoglycemia during periods of fasting since both glycogenolysis and gluconeogenesis are impaired. Primary treatment in North America consists of cornstarch therapy every 3-4 h. Waxy maize extended release cornstarch was introduced for maintaining overnight glucose concentrations, but no studies have assessed longterm safety and efficacy of the product.Objective: To demonstrate the safety and efficacy of modified cornstarch in GSD I.Design: An open-label overnight trial of extended release cornstarch was performed. Subjects with a successful trial (optimal metabolic control 2 or more hours longer than with traditional cornstarch) were given the option of continuing into the chronic observational phase. Subjects were assessed biochemically at baseline and after 12 months.Results: Of the 106 subjects (93 GSD Ia/13 GSD Ib), efficacy was demonstrated in 82 patients (88%) with GSD Ia and 10 patients (77%) with GSD Ib. The success rate for extending fasting was 95% for females and 78% for males. Of the patients who entered the longitudinal phase, longterm data are available for 44 subjects.

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Cornstarch Therapy in Type I Glycogen-Storage Disease

Cited by 294 publications

References 9 publications

Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer

Safety and Efficacy of Chronic Extended Release Cornstarch Therapy for Glycogen Storage Disease Type I

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