The GM1 Gangliosidosis one of the lipid storage diseases. It is caused by the storage of sugary lipids, the so-called gangliosides. Most gangliosides are deposited in the nerve cells.
What is GM1 gangliosidosis?
According to TOPBBACOLLEGES, GM1 gangliosidosis is a breakdown of GM1 gangliosides. This leads to the accumulation of this sugary lipid. Gangliosides generally consist of two fatty acid residues, which are linked to several sugar residues and an N-acetylneuraminic acid residue via the aminodialcohol sphingosine. A basic distinction must be made between GM1 gangliosides and GM2 gangliosides.
GM1 gangliosides contain four and GM2 gangliosides three sugar residues. The term ganglioside is derived from the terms ganglion and glycoside. A ganglion represents a nerve knot. Gangliosides are mainly found in the membranes of nerve cells. There they make up to six percent of the existing lipids. The hydrophobic part of the molecule with the fatty acid chains protrudes into the membrane, while the hydrophilic part with the sugar residues is outside the cell.
The exact meaning of the gangliosides is not yet known. According to available research results, they should be responsible for neural information transmission. There is a constant build-up and breakdown of gangliosides. However, if the breakdown is disturbed by an enzyme defect, the gangliosides accumulate in the nerve cells and cause considerable health problems. GM1 gangliosidosis occurs in infantile, juvenile and adult forms.
GM1 gangliosidosis is genetic. The starting point of the disease is a defect in the enzyme β-galactosidase. β-galactosidase is responsible for splitting off the sugar residues from the gangliosides. If this enzymatic step is disturbed, the GM1 gangliosides can no longer be broken down either. The GM1 gangliosides accumulate more and more in the nerve cells of the peripheral and central nervous system.
The three basic forms of GM1 gangliosidosis develop, depending on how severely the enzyme is restricted in its function. The condition is inherited as an autosomal recessive trait. The gene for coding β-galactosidase must have been passed on to the offspring from both parents. However, there are several mutations of the same gene that can lead to a defect or deficiency in β-galactosidase.
Symptoms, ailments & signs
The courses of the three forms of GM1 gangliosidosis are different. Infantile GM1 gangliosidosis is the most severe form with the worst prognosis, while adult GM1 gangliosidosis has the best prognosis. However, none of the three forms of disease can be cured. In any case, it is a progressive disease that can only be treated symptomatically.
Infantile GM1 gangliosidosis begins in the child’s first three months of life. From the sixth month of life onwards, development comes to a standstill. Symptoms such as hypotonia, poor drinking, reflux, weak bowel movements, pathological hypersensitivity to noises and severe liver enlargement occur.
The drinking weakness increases so dramatically that parenteral nutrition becomes necessary. The baby must be fed via infusions. Sometimes cerebral seizures also occur. Half of the children develop a cherry-red spot on the fundus. This happens because the retina turns whitish due to the storage of gangliosides and the macula therefore appears red.
The field of vision is severely clouded up to the point of possible blindness of the child. Furthermore, deafness can also occur. Changes to the bones are also detected. In rare cases, the tongue enlarges. The children usually die before the age of two from organ failure or constant infections. Infantile GM1 gangliosidosis is also known as Norman Landing syndrome.
The juvenile form of GM1 gangliosidosis, the so-called Derry syndrome, only begins after the first year of life. Here it comes to a hepatosplenomegaly, but it is less pronounced. Hepatosplenomegaly represents both liver and spleen enlargement. Further symptoms are hypotension, ataxia, convulsions, mental development disorders and spasticity. Furthermore, the facial features are becoming increasingly coarser.
The children usually die before the age of ten from respiratory diseases. There are only individual reports of the adult form of GM1 gangliosidosis. The onset of the disease is between the ages of three and thirty. These people experience dysarthria (speech disorders), gait disorders, and cramping. No precise information is yet available about the further forecast. The prognosis also depends on the rate at which the disease progresses.
GM1 gangliosidosis is diagnosed using human genetic or enzymatic examinations. The enzyme defect can be detected in the fibroblasts, leukocytes or through organ biopsies. GM1 gangliosidosis must be differentiated from oligosaccharidoses, sphingolipidoses and mucopolysaccharidoses in a differential diagnosis.
GM1 gangliosidosis leads to serious complications, which primarily have a negative impact on the child’s development or can even stop it completely. The development usually stops in the sixth month of the child’s life. There is a drinking weakness and the development of reflux disease.
The patient is also very sensitive to ordinary noises and suffers from a relatively large enlargement of the liver. The quality of life decreases enormously due to GM1 gangliosidosis and everyday life is made more difficult for the patient. Furthermore, complete hearing and vision loss can occur if the disease continues. In addition, the patient is more prone to infections and inflammation.
It is not uncommon for breathing difficulties to occur, which in the worst case can lead to a complete respiratory failure. The development stop also leads to a reduction in intelligence and weak motor skills. As a rule, the person concerned is then dependent on the help of other people.
Relatives and parents also suffer from psychological complaints from GM1 gangliosidosis, sometimes depression. A causal treatment of GM1 gangliosidosis is not possible. Life expectancy is drastically reduced by the disease.
When should you go to the doctor?
Parents who notice symptoms such as poor drinking, heartburn, hypotonia and a high sensitivity to noise in their child in the first three months of life should consult their pediatrician. The symptoms indicate a serious illness that needs to be clarified and, if necessary, treated. If there is a specific suspicion of GM1 gangliosidosis, a medical examination should be arranged immediately. A doctor’s visit is required at the latest when signs of an intestinal disorder or seizures are noticed.
External symptoms that need to be clarified include the characteristic cherry-red spot on the back of the eye. If there are visual or hearing impairments, medical advice is also required. In most cases, a specialist must be consulted for the respective condition in order to be able to make a clear diagnosis.
Depending on the form of the GM1 ganglion, the symptoms mentioned can appear three months after the birth or one year later. Unusual symptoms should therefore always be clarified medically. Especially children of parents who suffer from a genetic disease require extensive medical supervision.
Treatment & Therapy
A causal treatment of GM1 gangliosidosis is not possible. It is a genetic disease that is constantly progressing with the further storage of GM1 gangliosides. The disease can only be treated symptomatically and supportively. In the case of late onset GM1 gangliosidoses, enzymatic treatment is being discussed as a possible therapeutic approach. The slowness of the disease’s development means that there is greater therapeutic leeway here. However, there has not yet been a cure here either.
Outlook & forecast
Since scientists and doctors are not allowed to intervene in human genetics for legal reasons, there is currently no curability for GM1 gangliosidosis. The genetic disease can only be treated symptomatically by doctors, which is often a particular challenge. The prognosis of the disease is generally to be classified as unfavorable. Children experience a delay in their development in the first few years of life.
In severe cases, development stops prematurely, which has numerous consequences. The quality of life of the person affected is reduced, since in addition to the physical impairments, cognitive losses are also possible. Often it is not possible for the patient to cope with everyday life without sufficient help and support.
In exceptional cases, the patient is at risk of breathing difficulties, which can lead to a sudden stop of breathing. Therefore, GM1 gangliosidosis can be fatal. Without the use of medical care, the prognosis for the disease is even worse. The average life expectancy is significantly reduced due to the numerous complications.
Because of the sometimes very intense symptoms, the life of the person affected is immensely restricted. The nearby environment is also heavily burdened. Consequences and mental illnesses are to be expected, which lead to a further impairment of the quality of life and thus a poor overall prognosis.
To prevent GM1 gangliosidosis in the offspring of families in which cases of the disease have already occurred, genetic counseling is useful. The disease is inherited as an autosomal recessive trait. This assumes that both parents pass the mutated gene on to their children. For example, if both parents are healthy carriers of the mutated gene, their offspring have a 25 percent chance of developing GM1 gangliosidosis.
With GM1 gangliosidosis, in most cases there are no options for follow-up care available to those affected, as this disease is a hereditary disease that cannot be treated causally. The person affected is therefore entitled to purely symptomatic treatment, which, however, does not always lead to success.
If the patient wishes to have children, genetic counseling can be useful to prevent GM1 gangliosidosis from being passed on to offspring. GM1 gangliosidosis is usually treated with medication. In doing so, the person concerned must ensure that these medications are taken correctly and regularly, and the correct dosage must also be observed.
In cases of doubt or questions, a doctor should therefore always be consulted. In many cases, those affected by GM1 gangliosidosis are also dependent on intensive treatment and therapy, whereby they must be supported above all by friends and their own family.
In the case of psychological complaints, intensive and sensitive conversations with your own family are also very helpful. The parents of those affected often also need psychological treatment. The life expectancy of the patient is usually always restricted by GM1 gangliosidosis.
You can do that yourself
It is not possible to treat or support GM1 gangliosidosis through self-help measures. The patients are always dependent on symptomatic treatment, as causal therapy is usually not possible in this disease.
Since the disease could also be passed on, those affected or the parents should undergo genetic testing and counseling if GM1 gangliosidosis occurs in order to avoid passing it on to future generations.
The patients are always dependent on outside help in their everyday life. This help should preferably come from parents, relatives or friends, as this help always has a positive effect on the course of the disease. Help and support in everyday life is particularly important if you are blind or deaf. Children should be fully educated about GM1 gangliosidosis. This also includes education about the incurability of the disease.
If you have psychological problems, talking to people you know is always helpful. Contact with other sufferers of the disease can also have a positive effect on the course. In some cases, this also results in an exchange of information, which makes everyday life easier for the patient.