Aggressive therapy improves cirrhosis in glycogen storage disease type IX.

Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.

Bone mineral density in glycogen storage disease type Ia and Ib.

Purpose:The aim of this study was to characterize the pathogenesis of low bone mineral density in glycogen storage disease type Ia and Ib.Methods:A retrospective chart review performed at the University of Florida Glycogen Storage Disease Program included patients with glycogen storage disease type Ia and Ib for whom dual-energy X-ray absorptiometry analysis was performed. A Z-score less than -2 SD was considered low. Analysis for association of bone mineral density with age, gender, presence of complications, mean triglyceride and 25-hydroxyvitamin D concentrations, erythrocyte sedimentation rate, duration of granulocyte colony-stimulating factor therapy, and history of corticosteroid use was performed.Results:In glycogen storage disease Ia, 23/42 patients (55%) had low bone mineral density. Low bone mineral density was associated with other disease complications (P = 0.02) and lower mean serum 25-hydroxyvitamin D concentration (P = 0.03). There was a nonsignificant trend toward lower mean triglyceride concentration in the normal bone mineral density group (P = 0.1).In patients with glycogen storage disease type Ib, 8/12 (66.7%) had low bone mineral density. We did not detect an association with duration of granulocyte colony-stimulating factor therapy (P = 0.68), mean triglyceride level (P = 0.267), erythrocyte sedimentation rate (P = 0.3), or 25-hydroxyvitamin D (P = 0.63) concentration, and there was no evidence that corticosteroid therapy was associated with lower bone mineral density (P = 1).Conclusion:In glycogen storage disease type Ia, bone mineral density is associated with other complications and 25-hydroxyvitamin D status. In glycogen storage disease type Ib, bone mineral density was not associated with any covariates analyzed, suggesting multifactorial etiology or reflecting a small sample.Genet Med advance online publication 5 April 2012.

Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib.

PURPOSE: The aim of this study was to characterize the frequency and causes of anemia in glycogen storage disease type I. METHODS: Hematologic data and iron studies were available from 202 subjects (163 with glycogen storage disease Ia and 39 with glycogen storage disease Ib). Anemia was defined as hemoglobin concentrations less than the 5th percentile for age and gender; severe anemia was defined as presence of a hemoglobin <10 g/dl. RESULTS: In glycogen storage disease Ia, 68/163 patients were anemic at their last follow-up. Preadolescent patients tended to have milder anemia secondary to iron deficiency, but anemia of chronic disease predominated in adults. Severe anemia was present in 8/163 patients, of whom 75% had hepatic adenomas. The anemia improved or resolved in all 10 subjects who underwent resection of liver lesions. Anemia was present in 72% of patients with glycogen storage disease Ib, and severe anemia occurred in 16/39 patients. Anemia in patients with glycogen storage disease Ib was associated with exacerbations of glycogen storage disease enterocolitis, and there was a significant correlation between C-reactive protein and hemoglobin levels (P = 0.036). CONCLUSION: Anemia is a common manifestation of both glycogen storage disease Ia and Ib, although the pathophysiology appears to be different between these conditions. Those with severe anemia and glycogen storage disease Ia likely have hepatic adenomas, whereas glycogen storage disease enterocolitis should be considered in those with glycogen storage disease Ib.

Natural history of hepatocellular adenoma formation in glycogen storage disease type I.

OBJECTIVE: To characterize the natural history and factors related to hepatocellular adenoma (HCA) development in glycogen storage disease type Ia (GSD Ia). STUDY DESIGN: Retrospective chart review was performed for 117 patients with GSD Ia. Kaplan-Meier analysis of HCA progression among two groups of patients with GSD Ia (5-year mean triglyceride concentration ≤ 500 mg/dL and >500 mg/dL); analysis of serum triglyceride concentration, body mass index SDS, and height SDS between cases at time of HCA diagnosis and age- and sex-matched control subjects. RESULTS: Logrank analysis of Kaplan-Meier survival curve demonstrated a significant difference in progression to HCA between the 5-year mean triglyceride groups (P = .008). No significant difference was detected in progression to adenoma event between sexes. Serum triglyceride concentration was significantly different at time of diagnosis of adenoma (737 ± 422 mg/dL) compared with control subjects (335 ± 195 mg/dL) (P = .009). Differences in height SDS (P = .051) and body mass index SDS (P = .066) approached significance in our case-control analysis. CONCLUSION: Metabolic control may be related to HCA formation in patients with GSD Ia. Optimizing metabolic control remains critical, and further studies are warranted to understand the pathogenesis of adenoma development.