Inherited metabolic disorder characterized by
hepatosplenomegaly and failure to thrive during the first year of life,
followed by progressive liver cirrhosis with portal hypertension and death
by 5 years of age.
Amylopectinosis; Andersen Disease; Brancher Deficiency;
Glycogenosis type IV.
Also named Anderson Disease after the American pathologist and
pediatrician Dorothy Hansine Anderson (1901-1963) who described the disease in 1938.
GSD IV accounts for only 3% of all glycogen storage
diseases, which translates to an incidence of about 1:800,000-1,200,000 neonates.
Autosomal recessive. Both sexes are affected.
The disease is caused by defects in the gene coding for the
glycogen-branching enzyme located on chromosome 3p12.
Deficiency of amylo-1,4 to 1,6-transglucosidase
(glycogen-branching enzyme), which results in production of abnormal
glycogen with long, unbranched outer chains and decreased solubility
(amylopectin-like). Tissue glycogen concentration is usually not increased,
but the presence of insoluble glycogen induces foreign-body reactions,
leading to cellular injury and organ dysfunction. Ultimately, patients
develop terminal hepatic cirrhosis. In skeletal muscles, the presence of
abnormal glycogen leads to weakness, exercise intolerance, and muscle
atrophy. Cardiac involvement yields to dilated cardiomyopathy and progressive
heart failure. In the nervous system, the presence of abnormal glycogen
results in cognition disorders and both neuromuscular and neurovisceral
Clinical features. Diagnosis of GSD IV relies on
demonstration of deficient glycogen-branching enzyme activity (1-10% of
normal values) by an indirect enzyme assay. Heterozygotes display an
intermediate reduction in enzyme activity. Definitive diagnosis may involve
biopsy of the liver or other affected organs for microscopic examination and
enzyme assay. Antenatal diagnosis consists of measuring the levels of
glycogen-branching enzyme activity in cultured amniocytes and chorionic
villi. Molecular diagnosis may be performed in selected cases.
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.
Assess for signs and symptoms of
cardiac failure. Obtain chest radiograph, ECG, ...