Accumulation 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. About 1 infant out of 7000-8000 newborns is born with pathologies of accumulation. These ailments are difficult and difficult to treat. In the article we will consider the classification of such diseases and their symptoms.
What it is
Every cell in the human body contains lysosomes. These organoids produce the enzymes necessary for the breakdown of various nutrients. Lysosomes play a major role in intracellular digestion.
As a result of gene mutations in newborns, the function of these cellular structures may be impaired. Because of this, an enzyme deficiency occurs in the body, and lysosomes cannot digest certain types of nutrients. This extremely negatively 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 a child’s disease of lysosomal accumulation. They occur with the same frequency in boys and girls. These are very serious pathologies that, without treatment, lead to disability and early death. Such diseases require lifelong therapy.
Hereditary accumulation 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 thesaurismosis
Consider the classification of diseases of accumulation. Such pathologies are divided into several groups depending on the type of accumulating substances. Doctors distinguish the following types of hereditary metabolic disorders:
- sphingolipidoses;
- lipidoses;
- glycogenosis;
- glycoproteinoses;
- mucopolysaccharidoses;
- mucolipidoses.
Sphingolipidoses
Such accumulation diseases are characterized by impaired sphingolipid metabolism. These substances are responsible for the transmission of cellular signal. They are located mainly in the nervous tissue.
What happens when the metabolism of sphingolipids is impaired? These substances begin to accumulate in the liver, spleen, lungs, brain and bone marrow, which leads to severe organ dysfunction. The following pathologies belong to sphingolipidosis:
- Gaucher disease
- Tay-Sachs disease;
- Sandhoff disease;
- metachromatic leukodystrophy;
- gangliosidosis GM1;
- Fabry disease;
- crabbe disease;
- Norman Pick disease.
Symptoms of such pathologies depend on the localization of the accumulation of sphingolipids. The above diseases can be accompanied by the following manifestations:
- enlarged liver and spleen;
- hematopoiesis disorders;
- neurological disorders;
- mental retardation (in some cases).
Sphingolipidoses occur in about 1 out of 10,000 children. Gaucher disease is most common. Such children need lifelong enzyme replacement therapy. The later the manifestation of sphingolipidosis in the child occurs, the more favorable the prognosis.
Lipidosis
This group of pathologies includes Wolman disease and Batten's disease. These congenital ailments are accompanied by the accumulation of harmful fats in the tissues.
With Wolman's disease, cholesterol and triglycerides accumulate in the tissues. 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. At present, enzymatic preparations have been developed that alleviate the condition of the child.
Butten's disease proceeds with more severe symptoms. In neurons, the product of fat oxidation, lipofuscin, accumulates. This leads to death of nerve cells and severe disorders of the central nervous system: seizures, loss of ability to walk and talk, loss of vision. Currently, no effective methods of treating this pathology have been developed. Butten's disease most often leads to the death of the child.
Glycogenosis
In diseases of glycogen accumulation, the patient lacks the enzyme glucosidase. This leads to the fact that polysaccharide substances begin to be deposited in the tissues. Accumulation of glycogen is noted in muscles and neurons, which leads to serious damage to cells.
Glycogenosis includes Pompe disease. This pathology is most often manifested in children aged 4-8 months. It is accompanied by the following symptoms:
- The baby’s muscles look normal, but they are very weak and lethargic.
- It becomes difficult for the child to hold his head.
- The baby cannot roll over, its movements are difficult due to muscle weakness.
Over time, the child has a lesion of the heart muscle. Without treatment, this disease leads to death from respiratory and heart failure.
In some cases, signs of Pompe disease appear in children at a later age (1-2 years). In a child, the strength of the muscles of the arms and legs decreases. In the future, the pathological process extends to the muscles of the diaphragm, which leads to respiratory failure and can cause death.
The only way to treat this disease is with replacement therapy with the Mayozime drug. This medicine helps make up for glucosidase deficiency and improves glycogen metabolism.
Glycoproteinosis
Glycoproteinoses are accumulation diseases in which complex carbohydrates are deposited in the tissues. These substances affect neurons, which leads to serious neurological disorders. Such pathologies include:
- Mannosidosis If the child is completely lacking the mannosidase enzyme, this leads to death in infancy. The cause of death is severe neurological disorders. If the activity of the enzyme is slightly reduced, then the patient has a sharp decrease in hearing and mental disorders.
- Sialidosis In patients, a deficiency of the enzyme neuraminidase is formed. The disease is accompanied by twitching of the muscles, impaired gait, a sharp deterioration in vision.
- Fucosidosis The disease is associated with a deficiency of the hydralase enzyme. Patients have a delay in psychomotor development, trembling of the extremities, convulsions, skull deformities, and thickening of the skin.
There are no effective treatments. Only symptomatic therapy is possible that alleviates the condition of the child.
Mucopolysaccharidoses
Mucopolysaccharidoses (MPS) are accumulation diseases in which undigested acid glycosaminoglycans are deposited in the connective tissue. These compounds are otherwise called mucopolysaccharides. They adversely affect the state of neurons, bones, internal organs and tissues of the eye.
Currently, the following types of MPS are distinguished:
- Gurler, Sheye and Gurler-Sheye syndrome;
- Hunter syndrome
- Sanfilippo syndrome;
- Morkio syndrome;
- Maroto-Lamy syndrome;
- Sly's syndrome;
- Di Ferrante syndrome;
- Natovich syndrome.
In the most mild form, Cheye, Hunter, and Morkio syndromes occur. 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 growth;
- rude, grotesque features;
- deformations of the skeleton;
- damage to the heart and blood vessels;
- impaired vision and hearing;
- enlarged liver and spleen;
- impaired intelligence (with some types of MPS).
Currently, enzymatic replacement therapy has been developed for only four types of MPS - Gurler, Sheye, Hunter and Maroto-Lami syndromes. In other forms of mucopolysaccharidoses, patients are shown symptomatic treatment.
Mucolipidoses
Mucolipidoses are accumulation diseases in which a deficiency of the phosphotransferase enzyme is formed in the body. Such pathologies are accompanied by deposition in the tissues of mucopolysaccharides, oligosaccharides and lipids. Defective lysosome enzymes are found in the blood of patients.
This group of pathologies includes I-cell disease. It manifests itself most often before the age of 1 year. The child has the following symptoms:
- rude facial features;
- thickening of the skin;
- skeleton deformities;
- congenital dislocation of the hip;
- enlarged spleen and liver;
- frequent colds;
- lag in psychomotor development.
Currently, the treatment of this disease has not been developed. Prevention of the birth of a sick child is possible only with the help of prenatal diagnosis.
Conclusion
Accumulation diseases in children usually do not appear immediately after birth. Pathological signs can occur 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 the child.
Currently, replacement therapy has been developed for some hereditary metabolic disorders. It consists in the lifelong intake of missing enzymes. Such treatment is very expensive. It cannot save a child from a gene mutation. However, enzymatic therapy can stop the progression of the disease and extend the life of the patient.