Sialic acid storage disease is a very rare, genetically determined lysosomal storage disease in which the protein sialin is incorrectly encoded. Sialin is a transmembrane protein that normally clears the lysosome of monosaccharides such as sialic acid, which result from the enzymatic breakdown of glycoproteins and other substances. The reduced functionality of the sialin leads to an accumulation of sialic acid in the lysosomes, i.e. to sialic acid storage disease.
What is Sialic Acid Storage Disease?
The term sialic acid includes derivatives of neuraminic acid that are N- or O-acetylated. Sialic acids are building blocks of glycoproteins, glycosaminoglycans and other substances and are released through their enzymatic degradation within special lysosomes. For pco syndrome in dictionary, please visit dictionaryforall.com.
Normally, the sialic acids are transported out of the lysosome through the membrane of the lysosome with the help of the anion transport protein sialin. Characteristic of the sialic acid storage disease, which is also referred to as neuraminic acid storage disease, is a functional restriction or a total loss of function of the transport protein sialin.
The sialic acids produced in the lysosomes can be smuggled out of the lysosomes, resulting in an excessive accumulation of sialic acids in the lysosomes. An infantile and an adult form of the lysosomal sialic acid storage disease are known. The adult form is also known as Salla disease.
The causes of the loss of function of the transmembrane protein sialin in the infantile as well as in the adult form can be traced back to a defect or a mutation in the SLC17A5 gene. The gene is on chromosome 6, on gene locus q14-q15. All known mutations in the gene lead to incorrect coding of the protein sialin.
Although it is accepted by the metabolism as a building block, it does not have the ability to eject the sialic acid through the lysosomal membrane. The wrong coding of the sialin gives the protein a different tertiary structure, which is associated with the loss of its ability to function as a transport protein. Different gene mutations lead to infantile or adult forms of sialic acid storage disease.
Symptoms, Ailments & Signs
Of the two forms, infantile sialic acid storage disease is the one with the less favorable prognosis. The first signs and symptoms already manifest before birth. So-called hydrops fetalis, an accumulation of tissue fluid that extends over large parts of the fetus, can usually be detected in prenatal diagnostics using ultrasound.
Postnatal enlargement of the liver and spleen is symptomatic, and facial features are usually coarse. Life expectancy in the infantile form of neuraminic acid storage disease is usually just a few years. Salla disease, or the adult form of sialic acid storage disease, becomes apparent as early as infancy.
This occurs through muscular hypotonia and horizontal nystagmus, in which the eyes make jerky horizontal movements. Those affected show mental disabilities and mostly do not have the ability to speak. The prognosis for life expectancy is slightly more favorable than with the infantile form of the disease. Those affected usually reach adulthood.
Diagnosis & course of disease
In people affected by sialic acid storage disease, an increased concentration of sialic acid in the urine is symptomatic and an increased rate of excretion of polysaccharides. Free sialic acid can be detected in fibroblasts and amnion cells. A genetic test, which can also be carried out prenatally, serves as the last certainty.
In severe cases of sialic acid storage disease, bone malformations, ascites ( abdominal dropsy ), severe movement disorders, spastic cramps and severe mental disabilities become noticeable soon after birth. The severe forms of the disease lead to death in early childhood.
In the case of moderately severe courses – such as are typical for Salla disease – those affected usually reach adulthood. Symptomatic for these progressive forms are a severe intellectual disability, spastic convulsions and severe psychomotor limitations. Although the disease is very rare worldwide, it shows a regional focus in northern Finland, where one in 40 heterozygous carriers is one of the relevant gene mutations.
In most cases, sialic acid storage disease can be recognized and diagnosed before birth. Those affected usually suffer from a significantly enlarged spleen and liver. This can lead to pain in the respective regions. The facial features of the patients are often coarse, so that teasing or bullying can occur, especially at a young age.
Many children suffer from mental health problems or depression. Furthermore, those affected often also suffer from mental disabilities and thus also from restrictions in everyday life. They are therefore often dependent on the help of other people in their everyday life and cannot easily carry out many everyday things. Likewise, the sialic acid storage disease can lead to speech problems, so that the communication of those affected is also significantly restricted.
Due to the sialic acid storage disease, the life expectancy of the patient is usually also considerably reduced. Most of those affected only survive to adulthood. Since a causal therapy is not possible, only the symptoms can be limited. However, there are no particular complications. Sialic acid storage disease cannot be prevented.
When should you go to the doctor?
Sialic acid storage disease usually always requires medical examination and treatment. Since this is a hereditary disease, a genetic test should also be carried out if you wish to have children in order to prevent the disease from being passed on to the descendants. Since this does not lead to self-healing, the person affected by the sialic acid storage disease is dependent on lifelong treatment by a doctor in any case.
A doctor should be consulted if the patient suffers from a significantly enlarged spleen or liver. In most cases, these ailments are only discovered incidentally through an ultrasound examination, although pain in the sides of the body can also indicate these ailments. In some cases, speech problems or a number of mental disabilities also indicate sialic acid storage disease.
The first examination of this complaint can be carried out by a general practitioner. Further treatment is usually carried out by various specialists and always depends on the exact symptoms.
Treatment & Therapy
Since the sialic acid storage disease is based on a genetic defect, a causal therapy is not possible. There is no way to replace the functionally impaired transmembrane and anion transport protein with functional sialin. The possible therapies are (still) limited to treating the symptoms and ensuring that the patients suffer as little pain as possible.
In the case of some other lysosomal storage diseases, such as Hunter ‘s and Gaucher’s diseases, the administration of genetically engineered enzymes by infusion has already shown positive results. The procedure is known as enzyme replacement therapy and is shown in internal organs and in connective tissue. Due to their size, the artificially supplied enzymes cannot cross the blood-brain barrier, so that such therapies have no influence on developments in the CNS.
A form of therapy that is still in its infancy is what is known as gene therapy, which is intended to lead to a targeted replacement of the mutated gene sequence. In principle, this is a technique that is used in a positive sense in the body’s own gene repair or can also have a negative effect in the form of certain pathogenic germs.
Preventive measures that could prevent the onset of sialic acid storage disease are not available because it is a genetic, systemically effective disease that is created prenatally.
In families in which, for example, cases of Salla’s disease have become known, a genetic test can be used to determine whether the potential parent is a carrier of one of the known gene mutations without being ill themselves. In the positive case, a counseling interview should be held in which the risks that exist for the child if the desire to have children is realized are explained.
As a rule, patients with sialic acid storage disease have no special options for direct follow-up care. For this reason, this disease should be diagnosed and treated by a doctor at an early stage, so that there are no complications or other symptoms in the further course.
The sooner a doctor is consulted, the better the further course of this disease, so that a doctor should be contacted as soon as the first signs and symptoms appear. As a rule, self-healing cannot occur in the case of sialic acid storage disease. Most patients with sialic acid storage disease are dependent on taking different medications in order to permanently and properly relieve the symptoms of the disease.
Regular intake and the prescribed dosage must be observed in order to counteract the symptoms correctly. Regular check-ups by a doctor are also very important in order to identify and treat other damage early on. Some of those affected are also dependent on the help and support of their own families due to the disease. This disease may also reduce the life expectancy of the patient.
You can do that yourself
Since the disease is based on a genetic defect, those affected cannot take any measures to help heal the health disorder. The self-help measures should focus on improving daily processes and well-being.
It must be taken into account that a large number of patients suffer from a limitation in cognitive performance. They are therefore often dependent on the help and support of relatives or medically trained nursing staff. When coping with the disease, parents or other family members in particular must ensure that they take their own limits into account and do not give up on themselves in the care and support. The construction of elements to improve the joy of life is immensely important for everyone involved. A stable social environment also helps with adversity.
Since the disease has a negative effect on the development of some organs, this should be taken into account in everyday life. A healthy diet, optimal sleep hygiene and regular daily routines help to cope with the disease. They bring security and stability. Since the patient’s communication is limited, possibilities should be developed so that a good exchange between all those involved can take place in everyday life. Mutual understanding, calmness and the avoidance of hectic are conducive to further development.