Pictorial Review of MRI Findings of Glycogen Storage Disease from Children to Young Adults

3. MRI Findings of Complications Associated with GSDs

3.1. Hepatic Involvement

Hepatomegaly is observed even in young children with GSDs because of the early accumulation of glycogen (Figure 5) [3,5,6]. Hepatosplenomegaly occurs as hepatic dysfunction progresses, and ultimately liver transplantation can be performed [1]. MRI is useful for monitoring the size and morphology of the liver and spleen and making a diagnosis of liver cirrhosis.

Hepatic steatosis is often associated with GSDs because of malnutrition and lipid metabolism disorders [3,6]. Dual-echo T1-weighted imaging reveals hepatic steatosis (Figures 6A and 7A) [9]. It is also useful for monitoring the severity of hepatic steatosis. The liver signal normalizes on opposed-phase T1-weighted imaging in patients with GSD type I following successful dietary therapies (Figure 6B).

Regenerative nodules are associated with liver cirrhosis. Gd-EOB-DTPA enhanced imaging is useful for differentiating hepatic nodules, and regenerative nodules show high signal intensity in the hepatobiliary phase (Figure 9) [17]. As the liver parenchymal damage progresses, the number of regenerative nodules increases, as identified by MRI (Figure 9B).

Hepatic adenoma and adenomatosis are common complications of GSDs [1,2,3,6,7,8]. Some genetic alternation may contribute to a larger hepatic adenoma in patients with GSD type Ia [3]. Different from hepatic adenomas without GSDs, those associated with GSDs are often found in male patients and multiple lesions (i.e., hepatic adenomatosis) and increase in size (Figures 3B, C, 7B and C) [17,18]. The hepatic adenoma associated with GSDs are not related to contraceptives. It is clinically problematic to differentiate between a growing hepatic adenoma and hepatocellular carcinoma. Indeed, hepatic adenoma can transform into hepatocellular carcinoma in the older patients with GSDs, exhibiting similar imaging appearances in GSDs (Figures 3C, 7B and 8) [9,17]. Multimodality imaging surveillance should be performed once a hepatic tumor presenting strong enhancement in the arterial phase is identified in patients with GSDs [6,9].

3.2. Renal Impairment

Glycogen and similar materials accumulate in the kidneys, which induces renal complications in patients with GSDs [1,2,3,5,14]. MRI is insensitive to renal calculi associated with GSDs, whereas it can detect enlargement or atrophy of the kidneys (Figures 2A and 3A). T1-weighted imaging identifies renal impairment as decreased corticomedullary contrast in the kidneys (Figure 2A) [15]. MRI can also be used to investigate transplanted kidneys without contrast agents (Figure 2B).

3.3. Skeletal Muscular Growth Retardation

Glycogen is consumed in skeletal muscles during physical activity. Growth retardation, atrophy, and clinical symptoms, including muscular weakness and cramping, are observed in children and young adults with GSDs [1,2]. MRI may be useful for evaluating the volume and fatty infiltration in skeletal muscles (Figure 6B). Because MRI can visualize the distribution of involved muscles in a wide range of view, it may be useful for distinguishing GSDs from muscular dystrophies and neuromuscular disorders [19].

3.4. Myocardial Involvement

GSD type IIIa is known to involve the myocardium and can lead to sudden cardiac death because of severe myocardial hypertrophy or glycogen accumulation in the conduction system [1,2,4]. MRI is the best imaging tool for evaluating tissue characterization of the myocardium. Myocardial edema and scars associated with GSD type IIIa are visualized with T2-weighted and LGE imaging, respectively (Figure 4) [10,11,12,16]. LGE is useful for observing myocardial scars that can progress even after liver transplantation (Figures 4B and C). Differential diagnoses of myocardial involvement in GSD include hypertrophic cardiomyopathy, Anderson-Fabry disease, Noonan syndrome, and mitochondrial cardiomyopathies, which exhibit myocardial hypertrophy in children and young adults [11,20,21].

4. Future Directions

MRI is useful for observing the whole body with high spatial and contrast resolution, a wide range of views, and no need for radiation. Tobaly et al. [19] have applied whole-body MRI to investigate the distribution and severity of skeletal muscles involved by GSD type III.

Some quantitative MRI techniques can be applied to GSDs to evaluate their severity. Chemical shift exchange sequences and ¹³C MR spectroscopy can be used to estimate glycogen in the organs [22,23]. The Dixon sequence can be used to quantify hepatic steatosis associated with GSDs, because it is an established technique for measuring fat fraction in the liver [3,24]. Quantitative T1 mapping is used to evaluate myocardial fibrosis and edema in patients with GSD IIIa [12,25]. Because T1 mapping does not require gadolinium contrast agents for myocardial tissue characterization, it may be useful for patients with GSD and renal impairment [25]. T1 mapping may also be used to evaluate the fat fraction or degree of fibrosis in the liver [26].

5. Conclusions

GSDs, which are rare, inherited metabolic disorders of glycogen metabolism, involve multiple organs from childhood to young adulthood. In this pictorial essay, we reviewed MRI features of their complications to guide and monitor appropriate treatments for GSDs. Because some of these complications predict an unfavorable prognosis in pediatric patients with GSDs, radiologists should be able to recognize them with MRI.