Clinical heterogeneity with variable age of
onset, specific organ involvement, and degree of accumulation of abnormal
glycogen in different tissues. Typically, GSD IV patients present with
hepatosplenomegaly and progressive development of cirrhosis and portal
hypertension. Death commonly occurs before 5 years of age from hepatic failure.
Liver transplant may stop disease progression in some patients. Liver
disease may be associated with hypoalbuminemia, coagulopathy, and
thrombocytopenia. Esophageal varices, ascites, splenomegaly, renal failure and
hepatic encephalopathy may complicate the clinical course.
Associated features described in some patients include
cardiomyopathy with congestive cardiac failure, peripheral neuropathy, and
hypoglycemia. Prolongation of the QT interval on the ECG has been described
and may predispose to arrhythmias. Several neuromuscular forms of GSD IV
have been identified. A common variant consists of the development of
myopathy or cardiomyopathy during childhood. A perinatal form is
distinguished by severe neuromuscular involvement and death. Some patients
with clinically diagnosed adult polyglucosan body disease have deficient
glycogen-branching enzyme activity and diffuse neurologic (central and
peripheral nervous system) dysfunction. After liver transplantation, some
patients continue to have progressive accumulation of abnormal glycogen in other
organs, ultimately leading to death.