Type IV glycogenosis, Andersen 's disease (Glycogen storage disease type IV, Andersen disease) - Gen GBE1.
The type IV (GSD IV) glycogenosis, also called Andersen disease, is an inherited disorder caused by the accumulation of glycogen in the body cells. Accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. They described five types of glycogen storage disease type IV, which differ in their severity, signs and symptoms.
The perinatal fatal neuromuscular type is the most severe form of GSD IV. Signs and symptoms of this type manifest before birth. Excess liquid may accumulate around the fetus and in the body of the fetus. Affected fetuses have a condition called fetal akinesia deformation sequence, causing a decrease in fetal movement and can lead to arthrogryposis after birth. Children with perinatal fatal neuromuscular type manifest severe hypotonia and atrophy. These children usually do not survive beyond the neonatal period due to the weakness of the heart and respiratory muscles.
Congenital muscular type of GSD IV is usually not evident before birth but develops in early childhood. Affected children have severe hypotonia, which affects the respiratory muscles. Often these newborns have dilated cardiomyopathy, which prevents the heart to pump blood efficiently. Children with congenital muscular type of GSD IV usually survive only a few months.
The progressive liver type is the most common form of GSD IV. Within the first months of life, newborns affected have difficulty gaining weight, growth retardation and hepatomegaly. Children with this type develop cirrhosis often is irreversible. In addition, these individuals may manifest portal hypertension, ascites and hypotonia. Often, children with progressive liver type die of liver failure in early childhood.
The non - progressive liver type IV GSD has many of the characteristics of progressive liver type, but liver disease is not as severe. In the non - progressive liver type, hepatomegaly and liver disease are usually evident in early childhood, but affected individuals usually do not develop cirrhosis. People with this type may also have hypotonia and myopathy. Most people with this type survive to adulthood, although life expectancy varies depending on the severity of signs and symptoms.
Child neuromuscular GSD type IV develops in later childhood and is characterized by dilated cardiomyopathy and myopathy. The severity of this type varies greatly: some people only have mild muscle weakness while others have severe cardiomyopathy and die in early adulthood.
IV glycogenosis type, is due to changes in the GBE1 gene, located on the short arm of chromosome 3 (3p12.3). This gene encodes racemase glycogen. This enzyme is involved in the last stage of the production of glycogen. Some of the glucose molecules that make up the glycogen are joined together in a straight line, while other branch of the main chain and side chains formed. The enzyme glycogen racemase is involved in the formation of these side chains. The branched structure of glycogen makes it more compact for storage and allows to decompose more easily when needed as an energy source.
They have identified approximately 40 mutations in the gene responsible for GBE1 glycogenosis type IV (GSD IV). Most mutations change individual amino acids in the racemasa glycogen. These changes result in a severe deficiency or total absence of glycogen racemasa. As a result, polyglucosans bodies accumulate in cells, leading to cell damage and death. These bodies accumulate in cells throughout the body, but the liver cells and muscle cells are the most affected in the GSD IV. Glycogen accumulation in the liver interferes with the functioning of the liver, causing liver disease and liver enlargement. The inability of muscle cells to break down glycogen causes muscle weakness and atrophy. In general, the severity of the disease is linked to the concentration of functional racemase encoded glycogen. People with fatal neuromuscular perinatal type tend to encode less than 5% of the enzyme, while those with child neuromuscular type may have about 20% of functional enzyme. The other types, are usually associated with between 5% and 20% of available functional enzyme. However, these estimates vary between different types.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with type IV glycogenosis (GSD IV), by complete PCR amplification of exons GBE1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).