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

Purpose 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.