α-Mannosidosis

α-Mannosidosis

α-Mannosidose is a very rare lysosomal storage disease in which the accumulation of the sugar mannose in the tissue plays a major role. The disease is hereditary and progresses inexorably. There are some very promising therapeutic approaches, but they are only in the early stages.

What is α-mannosidosis?

Alpha -mannosidosis is a lysosomal storage disease. With this disorder, so-called glucoconjugates, which are formed from the sugar mannose and certain proteins, accumulate in all body cells. Glucoconjugates are glucoproteins that normally have to be broken down in order for cells to function properly. For what is the definition of pi, please visit healthknowing.com.

In the case of α-mannosidosis, however, this degradation does not take place or only to an insufficient extent. As a result, the cells literally clog up with the waste products of mannose. The permanent storage of the glucoconjugates takes place in the so-called lysosomes. Lysosomes are cell organelles in which biopolymers are usually converted into monomers.

This requires special enzymes. The lysosomes are structures in which the recycling of high-polymer waste materials takes place. If the waste materials are no longer broken down, they continue to accumulate in the lysosomes and thus constantly increase the volume of the cells. There is no chance of naturally reducing the cell volume again.

For this reason, the functional limitations of the affected cells become more and more severe over time. These restrictions are irreversible. For the effective treatment of lysosomal storage diseases, research projects are looking for ways to initiate a process in which the stored substances can then be broken down again.

Alpha-mannosidosis is an extremely rare disease. According to preliminary estimates, only two children in every million live births are affected by this disease.

Causes

The cause of α-mannosidosis lies in the inability of the enzyme α-mannosidase to function. This enzyme is normally responsible for the breakdown of mannose glucoconjugates. However, if it is defective due to a gene mutation, it cannot fulfill its function, or not sufficiently.

The gene encoding this enzyme is known as the MAN2B1 gene and is located on chromosome 19. The gene defect, which leads to the failure of α-mannosidase, is inherited in an autosomal recessive manner. This means that the affected person must have two defective genes. Both parents are therefore carriers of this mutated gene, without them having to be ill themselves.

Symptoms, Ailments & Signs

α-mannosidosis is characterized by a variety of symptoms. Cases of illness with special courses are known. However, the main symptoms are immunodeficiency, hearing loss, skeletal changes, facial abnormalities, and intellectual developmental delays.

What all sufferers have in common is that the disorder continues to progress inexorably without any chance of healing. All symptoms worsen over time. The deafness increases. Due to the progressive skeletal changes, the patients are usually dependent on a wheelchair later on.

However, the disease takes an individual course in each patient. Some children are born with a clubfoot. Some develop hydrocephalus within the first year of life. Due to the immune deficiency, numerous poorly healing infections can occur in the first years of life, which in turn have a formative effect on the general course of the disease.

Deformations of the spine with the formation of scoliosis and changes in the sternum are common. An enlarged skull, widely spaced teeth, an enlarged tongue, and jaw malformations are often present. The motor function is disturbed by an existing muscle weakness and the skeletal anomalies.

In the majority of cases, there is increasing hearing loss, which usually necessitates the use of a hearing aid. In individual cases, the course of the disease is extremely unusual and can also be associated with psychotic disorders.

Diagnosis & course of disease

α-Mannosidosis can be diagnosed by determining the enzyme activity of α-mannosidase. If the activity of this enzyme in the leukocytes is very low, it is an α-mannosidosis. This result can also be confirmed by a genetic test.

Prenatal diagnosis of this disease is also possible. If an increased amount of oligosaccharides from mannose is measured in the urine, this is an indication that could point to α-mannosidosis. However, there are other causes that can lead to these elevated values.

When should you go to the doctor?

Α-mannosidosis is a genetic disease. Therefore, the first abnormalities are already present immediately after the birth. Conspicuous features of the physique, malformations or anomalies in the facial area indicate an existing disease. The clarification of the cause is necessary so that a diagnosis can be made.

In most cases, the birth takes place in the presence of an obstetric team. They notice the visual abnormalities of the infant and take further steps to provide health care. As the disease progresses, developmental delays usually occur. It is advisable to work with a doctor as soon as there are abnormalities in the movement sequences or mobility restrictions.

In the case of hearing loss, muscle weakness or abnormalities in the area of ​​the teeth and mouth, the person concerned needs medical care. People who suffer from a weak immune system should always consult a doctor. It is necessary to clarify the cause and, in addition, precautionary measures must be taken in good time to prevent secondary diseases from breaking out.

In addition, people who have been diagnosed with Α-mannosidosis within the family are advised to consult a doctor before planning offspring. Possible risks of inheritance should be discussed at an early stage. In this way, separate medical tests are already carried out during pregnancy.

Treatment & Therapy

A causal treatment of α-mannosidosis is not possible because the disease is genetic. However, a variety of symptomatic therapies are carried out to improve the quality of life. For example, it may be necessary to carry out orthopedic corrections in the event of joint changes.

As part of the therapy of α-mannosidosis, constant treatment of infections is also necessary. Physiotherapy is often carried out proactively. The administration of zinc sulfate can sometimes increase the residual activity of α-mannosidase, but this does not result in long-term success.

For some younger patients, allogeneic stem cell transplantation has proven itself. However, the disease must not be that far advanced at this point. The risks of this therapy must also be considered. A really promising therapeutic approach is enzyme replacement therapy, which has not yet progressed beyond the experimental stage. In animal experiments, the accumulation of mannoseoligosaccharides could be partially reduced by adding enzymes.

Prevention

Since α-mannosidosis is genetic, there are no preventive measures to prevent the disease. However, if cases of this disease have already occurred in the family, human genetic counseling can provide information about the risk for the offspring. Prenatal diagnosis of α-mannosidosis is also possible.

You can do that yourself

Alpha-mannosidosis is a serious disease that cannot be treated causally to date. Nevertheless, patients can take some measures to relieve the symptoms.

Visual aids and targeted vision training can help with visual problems. With early treatment, the typical squint can be reduced to such an extent that it is no longer a problem later in life. The diverse malformations must be treated surgically. These interventions represent a great burden, especially for the younger patients. Rest and bed rest are all the more important, later combined with moderate sport. Physiotherapy and talk therapies are essential components of the treatment and can be continued independently at home by those affected.

The α-mannosidosis reduces life expectancy and those affected are ultimately dependent on help in everyday life. The relatives of those affected should therefore try to find a nursing service or accommodation in a nursing home at an early stage. If the measures do not bring the desired success, the doctor is best consulted. A doctor specializing in hereditary diseases can provide advice on supportive care. If necessary, he can also establish contact with other affected persons.

α-Mannosidosis