Andersen disease represents a particularly severe form of glycogen storage disease. It is a hereditary disease characterized by the formation of an abnormal glycogen. The prognosis of the disease is very poor.
What is Andersen disease?
In Andersen disease, storage of an abnormal form of glycogen occurs. This glycogen is similar in structure to amylopectin, which is present in a high percentage in plant starch. Normally, glycogen is highly branched. In Andersen’s disease, however, only a weakly branched polysaccharide is present. Characteristic of the disease is rapid enlargement of the liver, which rapidly leads to cirrhosis. The abnormal polysaccharide can no longer be broken down and continues to accumulate. Responsible for the defective glycogen formation is the deficiency or even absence of the enzyme amylo-1,4-1,6-transglucosidase. It takes care of the branching in this polysaccharide molecule. The disease is very rare, but nevertheless occurs in various manifestations or forms. In the extremely severe form, the child is often stillborn. Mild forms that begin at a later age have also been described. In each case, however, there is a mutation in gene (GBE1), which is located on chromosome 3.
Causes
The cause of Andersen disease is a genetic defect in gene GBE1 on chromosome 3, which is inherited in an autosomal recessive manner. This gene is responsible for the synthesis of the enzyme amylo-1,4-1,6-transglucosidase. If this enzyme is missing or has limited function, normal glycogen can no longer be synthesized. The enzyme is responsible for the branching of the polysaccharose molecule. If this branching fails to occur or is only incompletely carried out, glycogen is formed that can no longer be broken down for rapid energy supply. On the contrary, it accumulates very quickly in the liver, spleen and lymph nodes. After each meal, part of the unused glucose is transported to the liver to store it as a reserve glycogen. However, this reserve substance cannot be used in its present form. The constant storage of the abnormal glycogen enlarges the liver and spleen more and more, leading to the inevitable destruction of both organs.
Symptoms, complaints, and signs
Andersen’s disease is manifested by extraordinary variability. True, it involves the constant storage of an abnormal glycogen, which cannot be broken down. But the expression of the disease can vary. Nevertheless, the prognosis of Andersen’s disease is overall very poor. The most prominent symptom is a constantly enlarging liver, which quickly develops into cirrhosis. The most severe form is already manifested by absent or decreased fetal movements before birth. The fetus shows signs of joint stiffness and lung hypoplasia. Usually, in these cases, the child is born dead. In classic cases, the child is still normally developed at birth. However, during the first months of life, hepatomegaly (enlargement of the liver) and muscle hypotonia (lack of muscle tone) develop. Overall, the child’s development is delayed. The disease progresses rapidly. The liver develops cirrhosis. There is also increased portal pressure and the spleen also enlarges. Due to the cirrhosis of the liver, varices develop in the esophagus with associated bleeding and abdominal dropsy. Death usually occurs in early childhood. In rarer cases, the disease begins later and shows symptoms of muscle weakness and heart failure. Neurologic symptoms also occur.
Diagnosis and course of the disease
The diagnosis can be made on the basis of the clinical picture and accompanied by laboratory tests, liver biopsies, and molecular genetic studies. Histologic examinations reveal the intracellular accumulation of stainable amylopectin-like structures. In hepatocytes, fibroblasts and leukocytes, the enzyme responsible is examined. A detected deficiency of amylo-1,4-1,6-transglucosidase confirms the diagnosis.
Complications
Usually, the child’s life expectancy is significantly reduced by Andersen disease, or the child is born already dead. This may result in severe psychological distress or depression, especially in the relatives or parents.In most cases, they are then dependent on psychological treatment. Affected children suffer from cirrhosis of the liver, which eventually leads to death. Furthermore, the joints are also stiffened and movements are no longer possible due to this complaint. The child’s mental development is also severely impaired by Andersen’s disease, so that those affected are usually always dependent on the help of other people. It is not uncommon for heart failure or muscle weakness to develop. Patients can also die of cardiac death. Unfortunately, Andersen’s disease cannot be cured. Even the transplantation of a liver can only alleviate the symptoms for a short time, since damage to the new liver will also occur. This eventually leads to the death of the child. However, the complaints and symptoms can be limited until then with the help of medical measures.
When should you go to the doctor?
Andersen’s disease is a genetic disorder that, in severe cases, can cause the fetus to die while still in the womb. Therefore, pregnant women should seek medical treatment as soon as irregularities or abnormalities are noticed during pregnancy. If the expectant mother has a vague feeling that something might be wrong with the unborn child, she should seek medical attention. If the newborn survives the first days and weeks after delivery, a doctor is needed as soon as any peculiarities become apparent in the further course of development. A visit to the doctor should be made if there is muscle weakness or disturbances in movement. Disturbances in growth are signs of a present illness and must be clarified. Abnormalities of the heart activity, deformations of the body as well as inconsistencies of a child’s behavior should be examined and treated. In many cases the disease leads to an enlargement of the organs. Especially the liver or spleen are affected in these cases. Therefore, a physician is needed as soon as there is an unusual shape of the upper body in direct comparison to infants or children of the same age. Discoloration of the skin or other irregularities of the skin appearance are other signs of health impairment. A yellowish face or yellowing of the eyes should be evaluated by a physician.
Treatment and therapy
Because the condition is genetic, no causative treatment can be given. Therapy is only symptomatic. As part of treatment, physicians focus mainly on complications that arise. Thus, the pressure in the portal vein circulation is lowered. Furthermore, a substitution of albumin and coagulation factors is carried out. In cases of liver failure, liver transplantation can prolong life. However, the disease cannot be cured even with a liver transplant. The genetic defect is present and will lead to deposits of the abnormal glycogen in the new liver as well. Storage of the defective polysaccharide also continues in the other organs of the so-called reticulohistiocytic system of the spleen and lymph nodes, so that severe complications may continue to occur even after successful liver transplantation. The reticulohistiocytic system is part of the immune system and includes the cells of the reticular connective tissue. These cells store particles and substances in order to break them down and then transport them out of the body. However, the degradation of the defective polysaccharose molecules is no longer possible here either.
Outlook and prognosis
Andersen disease offers a relatively poor prognosis. The metabolic disease has no cure to date and causes severe liver damage. In some cases, muscle symptoms and concomitant diseases occur, which progress progressively if left untreated. Life expectancy is considerably limited by the disease. Children with the disease reach the age of two to five on average. Early liver transplantation improves the prognosis. The prognosis is particularly poor in the classical forms of the disease, especially if liver transplantation is not performed in the first months of life. As a rule, the long-term prognosis is based on the extent, severity, and progression of the disease. Andersen’s disease is one of the most severe glycogenoses. Due to the liver complaints and other symptoms, the quality of life is usually greatly reduced. Pain medication and a comprehensive therapy improve the well-being of the child, but are in turn also associated with risks.The prognosis is determined by the liver specialist in charge. Life expectancy is considerably limited by the condition. Any concomitant diseases, as can occur with undiagnosed diseases, are also included in the prognosis. Andersen’s disease thus offers a poor prognosis overall. Novel treatments may provide improvement in the future.
Prevention
Prevention of Andersen disease can only relate to ensuring that offspring do not inherit the disease. Since Andersen’s disease is passed on in an autosomal recessive manner, several generations can be skipped in the inheritance. Therefore, if cases of Andersen’s disease have already occurred in the family and relatives, human genetic testing should be performed. If the gene is found in both parents, human genetic counseling is recommended. This is because there is a 25 percent chance for the offspring to develop Andersen’s disease in this case.
Follow-up
Since Andersen’s disease cannot be cured, the focus throughout the treatment period is on treating the symptoms or containing possible complications. Follow-up care is necessary, however, after procedures that are performed as part of the therapy. If a liver transplant is performed, professional aftercare is very important. This ensures that the new liver is not rejected by the body after the operation. Special drugs dampen the body’s immune response. As a result, however, the body’s resistance to pathogens is also weakened, which must be taken into account in further therapy. During this time, the patient must undergo regular blood checks. Care is taken to ensure that there are no rejection reactions or other serious complications such as kidney dysfunction, which can occur as a side effect. While the core symptomatology of Andersen’s disease can be improved immediately following liver transplantation, the deposition of the defective glycogen continues to occur, so that complications and progressive symptoms must be expected even after transplantation. In this regard, the liver specialist in charge can provide more detailed information about the prognosis and further course of treatment.
What you can do yourself
The self-help measures that a patient suffering from Andersen’s disease can take are limited to nonexistent. Because the disease has genetic causes and cannot be controlled despite symptomatic treatment, the sufferer’s options quickly become exhausted. He is best advised to take seriously and implement any dietary and lifestyle advice given by his attending physician. Furthermore, after a liver transplant, the patient should think about a gentle behavior. Alcohol, fatty foods and exertion should be avoided. This makes it easier for the body to really accept the new organ. However, a successful transplantation including successful aftercare cannot stop glycogenosis type 4 itself. Since it is an autosomal recessive disease (it can skip several generations), it makes sense to have a genetic profile done regarding family planning. While people affected by Andersen’s disease know about their gene anyway, an analysis in this regard is particularly worthwhile for family members. In this way, the transmission of the triggering gene can be prevented by adapted family planning. At the very least, however, certainty can be gained about the risk of disease in one’s own offspring.
