Storage Disease Metabolic Diseases

A considerable number of metabolic diseases cause liver injury in infants and children. In many cases, the liver is the sole organ clinically affected by the metabolic disease. In other metabolic diseases, other organs/tissues are affected but liver disease still constitutes a major cause of morbidity and mortality. Some of the diseases are relatively common. For instance, a-1-antitrypsin deficiency affects approximately 1 in 1,800 live births, while the incidence of cystic fibrosis is as high as 1 in 1,700 in some populations. Taken together, genetic/metabolic liver diseases account for approximately 30% of children who undergo liver transplantation.

In most cases, metabolic diseases affecting the liver ultimately lead to cirrhosis. Typically, the imaging findings in these cases are similar to those in adults in whom liver cirrhosis arises for other reasons. In other cases, however, the findings may be more subtle. Frequently hepatomegaly or fatty liver is the main finding during the early stages of disease.

Alpha-1-antitrypsin Deficiency. Alpha-1-antit-rypsin deficiency is the most common metabolic liver disease affecting children [94]. It also predisposes adults to HCC and causes emphysema, particularly in adults who smoke cigarettes. Recent studies have provided further information about the biochemical basis of the deficiency, and about the cellular mechanisms that account for the wide variation in phenotypic expression of liver disease. These studies have shown that this disease is pro-totypic for many genetic diseases associated with misfolded proteins and disturbances in the fundamental cellular pathways that respond to misfold-ed proteins, or stressors [95]. Recent studies have also provided evidence for the feasibility of chemoprophylaxis with a novel class of compounds called "chemical chaperones" that may have broad applicability to metabolic liver disease.

Glycogen Storage Disease. Another of the more common metabolic liver diseases is glycogen storage disease (GSD), a group of disorders that are associated with glycogen accumulation in the liver and other tissues due to specific defects in glycogenolysis. In this disease, mainly GSD type Ia is of interest with regard to imaging studies, since hepatomegaly with development of liver cell adenoma is a common finding. In GSD type Ia, there is developmental delay, hypoglycemia, metabolic aci-dosis, elevated triglycerides and uric acid levels in the blood, hepatomegaly, hepatic adenomas (Fig. 28), and HCC due to defects in the catalytic subunit of glucose-6-phosphatase. In GSD type Ib, the patients also have neutrophil dysfunction and recurrent infections due to a primary defect in a mi-crosomal glucose-6-phosphate transporter. In GSD type III, in which there is a defect in the glycogen debrancher enzyme, hepatomegaly occurs but liver dysfunction is rare. In GSD type IV, in which there is deficiency of the glycogen branching enzyme, there is progressive liver dysfunction and liver failure. GSD type VI is due to defects in liver phos-phorylase kinase. Nutritional therapy and the use of dietary cornstarch have had a major impact on GSD type Ia, whereas cytokine therapy has recently provided marked improvement in the lives of patients with GSD type Ib.

Wilson's Disease. A third common form of metabolic liver disease in children is Wilson's disease. It is a progressive disorder characterized by abnormalities of the motor system, psychiatric symptoms, and hepatic disease resulting in cirrhosis. A specific defect in copper transport results in progressive accumulation of copper in target tissues which leads to cirrhosis. Although copper is paramagnetic, substantial changes in liver SI are not found in patients with Wilson's disease. The main findings are liver cirrhosis and sometimes SI changes in the brain, especially the nucleus lentic-ularis, in which the concentration of copper may be much higher than in the liver.

Fig. 28a-c. Glycogenosis with multiple adenomas. The unenhanced CT scan (a) reveals multiple cysts and a tumor (arrow) surrounded by a hyperdense capsule. Following administration of contrast medium the lesion demonstrates strong hyper-vascularity surrounded by a rim on the arterial phase scan (b), followed by persistent enhancement in the portal-venous phase (c). Taken together with the history of glycogenosis, these imaging findings most likely depict liver adenoma

Fig. 28a-c. Glycogenosis with multiple adenomas. The unenhanced CT scan (a) reveals multiple cysts and a tumor (arrow) surrounded by a hyperdense capsule. Following administration of contrast medium the lesion demonstrates strong hyper-vascularity surrounded by a rim on the arterial phase scan (b), followed by persistent enhancement in the portal-venous phase (c). Taken together with the history of glycogenosis, these imaging findings most likely depict liver adenoma

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