Storage diseases are a group of hereditary pathologies accompanied by metabolic disorders. They are caused by mutations in the genes responsible for the activity of certain enzymes. Such diseases are quite rare. Approximately 1 infant out of 7000-8000 newborns is born with accumulation pathologies. These ailments are severe and difficult to treat. In the article we will consider the classification of such diseases and their symptoms.
What is this
Every cell in the human body contains lysosomes. These organelles produce the enzymes needed to break down various nutrients. Lysosomes play a major role in intracellular digestion.
As a result of gene mutations in newborns, the function of these cell structures can be impaired. Because of this, there is a deficiency of an enzyme in the body, and lysosomes cannot digest certain types of nutrients. This is extremelynegatively affects the state of the whole organism. Unsplit substances accumulate in tissues and organs, which leads to severe disorders of various body functions.
In such cases, doctors diagnose the child with lysosomal storage disease. They occur with equal frequency in boys and girls. These are very serious pathologies that, if left untreated, lead to disability and early death. Such diseases require lifelong therapy.
Hereditary storage diseases are called thesaurismoses. They are transmitted in an autosomal recessive manner. This means that the disease is inherited only if both parents are carriers of the damaged gene. The probability of having a sick child is 25%.
Varieties of thesaurismoses
Let's consider the classification of storage diseases. Such pathologies are subdivided into several groups depending on the type of accumulating substances. Doctors distinguish the following types of hereditary metabolic disorders:
- sphingolipidoses;
- lipidoses;
- glycogenoses;
- glycoproteinoses;
- mucopolysaccharidoses;
- mucolipidoses.
Sphingolipidoses
Such storage diseases are characterized by impaired metabolism of sphingolipids. These substances are responsible for the transmission of cellular signal. They are found predominantly in nervous tissue.
What happens when the metabolism of sphingolipids is disturbed? These substances begin to accumulate in the liver, spleen, lungs, head andbone marrow, which leads to severe disorders of organ function. Sphingolipidoses include the following pathologies:
- Gaucher disease;
- Tay-Sachs disease;
- Sandhoff disease;
- metachromatic leukodystrophy;
- gangliosidosis GM1;
- Fabry disease;
- Krabbe disease;
- Normann-Pick disease.
The symptomatology of such pathologies depends on the localization of the accumulation of sphingolipids. The above diseases may be accompanied by the following manifestations:
- enlarged liver and spleen;
- hematopoietic disorders;
- neurological disorders;
- mental retardation (in some cases).
Sphingolipidoses occur in about 1 in 10,000 children. Gaucher disease is the most common. These children require lifelong enzyme replacement therapy. The later the manifestations of sphingolipidoses appeared in the child, the more favorable the prognosis.
Lipidoses
This group of pathologies includes Wolman's disease and Batten's disease. These congenital ailments are accompanied by the accumulation of harmful fats in the tissues.
Cholesterol and triglycerides accumulate in the tissues in Wolman's disease. In the blood, the level of hepatic transaminases increases, which leads to fibrosis and cirrhosis of the liver in childhood. Marked dyspeptic symptoms and bloating are noted. Currently, enzymatic preparations have been developed that alleviate the condition of the child.
Batten's disease comes with more severe symptoms. The product of fat oxidation, lipofuscin, accumulates in neurons. This leads to the death of nerve cells and severe disorders of the central nervous system: convulsions, loss of the ability to walk and talk, loss of vision. Currently, there are no effective treatments for this pathology. Batten's disease most often leads to the death of a child.
Glycogenoses
In diseases of the accumulation of glycogen in the patient's body, the enzyme glucosidase is absent. This leads to the fact that polysaccharide substances begin to be deposited in the tissues. Accumulation of glycogen is observed in muscles and neurons, which leads to serious cell damage.
Glycogenoses include Pompe disease. This pathology is most often manifested in children aged 4-8 months. It is accompanied by the following symptoms:
- Baby's muscles look normal, but are very weak and sluggish.
- Baby finds it difficult to keep his head up.
- Infant cannot roll over and movements are difficult due to muscle weakness.
Over time, the child develops damage to the heart muscle. Without treatment, this disease leads to death from respiratory and heart failure.
In some cases, the signs of Pompe disease appear in children at a later age (1-2 years). The child has reduced muscle strength in the arms and legs. In the future, the pathological process spreads to the muscles of the diaphragm, which leads to respiratory failure and can cause death.
The only waytreatment of this disease is substitution therapy with the drug "Myozyme". This medicine helps replenish glucosidase deficiency and improve glycogen metabolism.
Glycoproteinoses
Glycoproteinoses are storage diseases in which complex carbohydrates are deposited in tissues. These substances affect neurons, leading to serious neurological damage. These pathologies include:
- Mannosidosis. If a child completely lacks the enzyme mannosidase, this leads to death in infancy. The cause of death is severe neurological disorders. If the activity of the enzyme is somewhat reduced, then the patient has a sharp decrease in hearing and mental disorders.
- Sialidosis. Patients develop a deficiency of the enzyme neuraminidase. The disease is accompanied by muscle twitching, gait disturbance, and a sharp deterioration in vision.
- Fucosidosis. The disease is associated with a deficiency of the enzyme hydralase. Patients have a delay in psychomotor development, trembling of the limbs, convulsions, deformities of the skull, thickening of the skin.
There are no effective treatments. Only symptomatic therapy is possible, which alleviates the child's condition.
Mucopolysaccharidoses
Mucopolysaccharidoses (MPS) are storage diseases in which uncleaved acidic glycosaminoglycans are deposited in the connective tissue. These compounds are otherwise called mucopolysaccharides. They adversely affect the state of neurons, bones, internalorgans and tissues of the eye.
Currently, the following types of MPS are distinguished:
- Gurler, Sheye and Gurler-Sheye syndrome;
- Hunter syndrome;
- Sanfilippo syndrome;
- Morquio syndrome;
- Maroteau-Lami syndrome;
- Sly syndrome;
- Di Ferrante syndrome;
- Natovich syndrome.
In the mildest form, Scheye, Hunter and Morquio syndromes occur. The life expectancy of patients can reach 35-40 years.
The most severe type of mucopolysaccharidosis is Hurler's syndrome. Sick children in most cases live no more than 10 years.
The clinical picture of mucopolysaccharidoses is characterized by the following manifestations:
- dwarf;
- rough, grotesque features;
- skeletal deformities;
- damage to the heart and blood vessels;
- impaired vision and hearing;
- enlarged liver and spleen;
- impaired intelligence (with some types of MPS).
Currently, enzyme replacement therapy has been developed for only four types of MPS - Hurler, Scheye, Hunter and Maroto-Lami syndromes. For other forms of mucopolysaccharidoses, symptomatic treatment is indicated for patients.
Mucolipidoses
Mucolipidoses are storage diseases in which a deficiency of the enzyme phosphotransferase is formed in the body. Such pathologies are accompanied by the deposition of mucopolysaccharides, oligosaccharides and lipids in the tissues. In the blood of patients, defective enzymes of lysosomes are found.
Bthis group of pathologies includes I-cell disease. It appears most often before the age of 1 year. The child has the following symptoms:
- rough facial features;
- thickening skin;
- skeletal deformities;
- congenital dislocations of the hip;
- enlarged spleen and liver;
- frequent colds;
- delay in psychomotor development.
There is currently no cure for this disease. The only way to prevent the birth of a sick child is through prenatal diagnosis.
Conclusion
Storage diseases in children usually do not appear immediately after birth. Pathological signs may appear at the age of several months, and sometimes only at 1-3 years. Previously, such diseases were considered incurable and often ended in the death of a child.
Replacement therapy for some hereditary metabolic disorders has been developed. It consists in the lifelong intake of the missing enzymes. Such treatment is very costly. It cannot save a child from a gene mutation. However, enzymatic therapy can stop the progression of the disease and prolong the life of the patient.
