Sandhoff’s disease is a lysosomal storage disease in which GM2 gangliosides are stored in the nerve cells. The enzyme activity of hexosaminidase A and B is restricted. The prognosis is usually very poor.
What is Sandhoff’s disease?
Sandhoff’s disease is one of the lysosomal storage diseases. The disease was first described in 1968 by the German biochemist Konrad Sandhoff. In this syndrome, GM2 gangliosides are accumulated in the nerve cells because two ganglioside-degrading enzymes are no longer able to function properly or at all. See growtheology for Comprehensive Guide to Hypercalcemia.
Gangliosides are water-insoluble lipids present in the membranes of all cells. Here they determine the structure of the outer part of the membrane. Chemically, they are made up of two fatty acid molecules bound to the amino dialcohol sphingosine. At the other end of the sphingosine molecule is an oligosaccharide made up of several sugar molecules.
The fatty acid residues protrude into the cell membrane towards the cell. This part of the molecule is non-polar and therefore fat-soluble. The sugar portion is on the surface of the cell membrane and interacts with polar molecules such as water. The accumulation of GM2 gangliosides occurs primarily in the nerve cells. A special function of gangliosides in the transmission of information between nerve cells is suspected there.
The gray matter of the brain is particularly rich in gangliosides. There they make up about six percent of all lipids. However, new gangliosides are constantly being formed, which normally have to be broken down again in order to remain in balance. In the case of Sandhoff’s disease, however, the degradation process is disturbed, resulting in an accumulation of gangliosides. The disease is very rare. A prevalence of 1 in 130,000 in Europe is given.
The cause of Sandhoff’s disease is the accumulation of GM2 gangliosides in the nerve cells. Two enzymes responsible for the breakdown of the gangliosides are restricted in their functionality or are completely inoperative. These are the enzymes hexosaminidase A and B. Both enzymes are encoded by the HEXB gene on chromosome 5. The corresponding mutation is at the point responsible for coding both proteins. As a result, there is a functional failure for both.
The hereditary defect is inherited in an autosomal recessive manner. In order for the disease to develop to its full extent, the corresponding genes in both parents must be defective. As a result of the degradation disorder, more and more gangliosides accumulate in the nerve cells. Finally, the function of the nerve cells is massively impaired as more and more ganglioside molecules are added.
The nerve cell keeps growing. This effect manifests itself in the gradual swelling of the brain. This disturbs the transmission of stimuli between the neurons. New connections between the neurons can no longer be formed and old connections are broken. As a result, mental decline sets in.
Symptoms, Ailments & Signs
As with many lysosomal storage diseases, Sandhoff’s disease is divided into several degrees of severity. These depend on the respective residual enzyme activity. There is an infantile, a juvenile and an adult form of the disease. In the case of the infantile form, the children develop after an inconspicuous development phase from the third month of life [developmental disorders in children|development delays]]. There is muscular hypotonia, frequent startle reactions and motor disorders.
In the further course, seizures, brain enlargement and declining vision are added. In late stages, vision is lost altogether. Mental and motor skills continue to decline. A cherry-red spot forms in the macula at the back of the eye. This progressive form usually ends fatally between the third and fifth year of life.
In the juvenile form, the first symptoms begin between the ages of two and five. The same changes occur here as well. However, the disease process progresses more slowly. The life expectancy here is between 15 and 20 years.
In the adult form, there are different symptoms that manifest themselves in neurological and psychiatric abnormalities. Vision and mental development may remain unaffected. The further course depends on the residual activity of the enzymes.
Diagnosis & course of disease
The enzyme activity of hexosaminidase A and B is determined to diagnose Sandhoff’s disease. If both enzymes show reduced activity, Sandhoff’s disease can be assumed. If there is only a functional restriction of the enzyme hexosaminidase A, it is Tay-Sachs disease, which takes a similar course. A genetic analysis can confirm the diagnosis.
Sandhoff’s disease causes significant limitations and delays in development, especially in children. This disease also leads to muscle wasting and also to swallowing difficulties. Normal intake of food and liquids is usually no longer possible for those affected due to the swallowing difficulties. Sandhoff’s disease also leads to motor disorders.
Patients often suffer from cramps and reduced vision. In the worst case, complete blindness occurs. The patient’s motor skills also decrease significantly as the disease progresses. Life expectancy is significantly reduced by Sandhoff’s disease, so that those affected usually live a maximum of 20 years.
Relatives and parents are also affected by Sandhoff’s disease and suffer from severe mental health problems or depression. The mental development of the patient is usually not affected by the disease. A causal treatment of Sandhoff’s disease is usually not possible. Some of the symptoms can be reduced with the help of therapies and medication. However, a complete cure of the disease is not possible.
When should you go to the doctor?
If unusual symptoms occur in early childhood or in old age, the doctor should always be consulted. A genetic analysis should be used to identify and differentiate between similar clinical pictures.
Since the hereditary Sandhoff’s disease is a neurodegenerative metabolic disease that usually occurs early, the first contacts with the doctor are often already given to small children affected. The previously untreatable disease leads to blindness and deterioration. Regular visits to the doctor are unavoidable in Sandhoff’s disease. The progressive lipid metabolism disease is one of the rare diseases. Since the affected children usually do not even reach the age of four, only symptomatic help can be offered.
The poor prognosis makes it difficult for parents of such children to deal with the disease. For the children themselves, not much can be done on the medical side. The degradation disorder causes more and more serious damage to the nerve cells. The brain is also badly affected. However, the severity of the disorder can vary. This influences the medical options for action.
With good treatment, juvenile Sandhoff’s disease can lead to a life expectancy up to puberty or beyond. Symptoms progress more slowly. They appear when they are about two years old. The adult form of Sandhoff’s disease is the one with the longest life expectancy. However, this is dependent on various influences in the enzyme area.
Treatment & Therapy
Unfortunately, a causal therapy for Sandhoff’s disease is not possible because the disease is hereditary. Only symptomatic treatments can be carried out. There are hopeful therapeutic approaches, but they are all only in the early stages. The prognosis is usually very poor.
Unfortunately, life expectancy cannot be extended today. In the adult form of the disease, however, the life expectancy of those affected is somewhat longer. However, it depends on the residual activity of the enzymes.
Outlook & Forecast
Sandhoff’s disease is a serious illness that is associated with severe symptoms for the sufferer and leads to death within a few months. The genetic disease therefore offers a relatively poor prognosis. The sick children usually die shortly after birth and suffer from severe physical limitations throughout their lives. On average, most Sandhoff disease patients die in their third or fourth year of life.
The first symptoms appear twelve to fourteen months before death and usually lead to the death of the child due to severe organ damage or cardiovascular problems. The genetic disease can only be treated symptomatically. If symptoms such as strabismus or nystagmus are treated adequately, the sick children can at least be able to lead a relatively symptom-free life. However, the regular visits to the doctor are associated with a lot of stress for the relatives and the patients themselves.
The quality of life is usually greatly reduced. Currently developed therapies could improve the prognosis in the future. In general, patients should follow the doctor’s assessments. The doctor gives an accurate prognosis with regard to the symptoms and the therapy options.
In families with members or relatives who suffer from Sandhoff’s disease, the prevention of the syndrome being passed on consists of extensive human genetic counseling. The disease is inherited in an autosomal recessive manner. This means that if both parents have the defective gene, there is a 25 percent chance of passing the disease on to their offspring.
First of all, the genetic status of both parents should be determined by means of a genetic test. If only one partner has the defective gene, the child is not at risk.
In most cases, the measures and the options for direct aftercare for Sandhoff’s disease are significantly limited or are not even available to the person concerned. For this reason, the affected person should consult a doctor very early on to prevent the occurrence of other complications or symptoms, since self-healing cannot occur in this case.
Likewise, if you want to have children again, you should see a doctor so that the children do not develop Sandhoff’s disease, as it is a hereditary disease. Those affected are dependent on taking medication that can alleviate and limit the symptoms. The doctor’s instructions must be followed, and a doctor must also be contacted if you have any questions or if you have severe side effects.
Furthermore, the correct dosage and the regular intake of the medication should be observed. Those affected by Sandhoff’s disease are often dependent on the help and care of other people in their everyday lives. Contact with other patients with the disease can also be very useful, as it is not uncommon for information to be exchanged.
You can do that yourself
The disease gives only a few options for action that patients or their relatives can use in everyday life. There is no cure for the genetic disease. Recovery can be achieved neither by conventional medicine nor by alternative means. Patients with Sandhoff’s disease have a significantly reduced life expectancy. In the area of self-help, the focus is ultimately on improving the quality of life.
Dealing with the symptoms and the course of the disease is particularly important in everyday life. The disease poses major challenges not only for the patient, but also for those around them. The mental strength is to be strengthened so that the circumstances can be processed well. In addition to the use of relaxation techniques, psychotherapeutic measures can help. In addition, relatives should take sufficient time to meet their own needs. This is the only way to ensure that they have sufficient resources when dealing with the sick child. Contacts to self-help groups or other sick people are felt to be helpful and supportive. In the exchange, mutual help for self-help takes place, as information and tips are given for coping with the situation.
To stabilize the organism, a healthy lifestyle and a balanced diet are advisable. The joy of life is to be promoted despite all adversities, so that an improvement in the overall situation is achieved.