Gaucher disease - a hereditary disease cumulative nature, which is one of the most popular among the lysosomal disorders.Gaucher disease develops due to glucocerebrosidase deficiency, which becomes the result of the accumulation of glucocerebroside in the tissues and some organs.
This disease belongs to a rare disease and manifests itself, according to statistics, relatively low.But, nevertheless, it may lead to disability and / or death at an early age, if not timely appropriate treatment initiated.
Gaucher disease causes
At the genetic level mutations occur in genes that are responsible for producing the enzyme glucocerebrosidase.This gene is localized with abnormalities on chromosome 1.These mutations are the cause of the low activity of the enzyme.Thus, there is an accumulation of glucocerebroside in the macrophages.
Mesenchymal cells, called Gaucher cells gradually grow and become hypertrophied.Since these cells occurring modifications, and they are located in the
Gaucher disease refers to an autosomal recessive disease.Therefore, any person can inherit a mutation of this enzyme with all the features in the same proportion as its father and the mother.Thus, the degree of severity of the disease and it will depend on the lesion genes.
Theoretically, each person may inherit a gene glucocerebroside with lesions or completely healthy.As a result of inheriting the gene abnormalities, there is a mutation of the enzyme, but it still does not mean the disease.But when the child receives two affected genes, then put the diagnosis of Gaucher disease.When the inheritance of the affected gene, the child is considered to be only a carrier of the disease, so there is a possibility of transmission of this feature, with hereditary diseases, to future generations.Thus, the carriers of the disease when both parents, the child may be born with Gaucher disease in 25% of cases, the child carrier - 50% and healthy - 25%.
incidence of this genetic disease among ethnic races is 1: 50,000, but more often it is detected among Ashkenazi Jews.
Gaucher disease is also called storage diseases due to lack of the enzyme, which is to withdraw the harmful products of metabolism from the body instead of accumulating them.As a result, these substances are collected in some organs the macrophages and destroy them.
Gaucher disease symptoms
clinical picture of the disease is characterized by three types.
In the first type of Gaucher disease nervous system is not involved in the accumulation of lipids, so it relates more to the flow of hematological diseases.First of all, there is an increase of many parenchymal organs, foremost among which is the spleen, and then visually observed by the deformation of bones.More often than not, this type of disease progression in adults.
infant, or the second type of Gaucher disease is characterized by acute neurology and diagnosed, mainly to six months of age.In this case, there are very early neurological symptoms characteristic, in which the stem cells of the brain are damaged, causing death in children.
third type of Gaucher disease - a juvenile form of the disease with subacute neyrovistseralnym type.At the beginning of the pathological process develops splenomegaly and mental retardation that affects pyramidal and extrapyramidal system of the brain.
Gaucher disease has a major change in the form of destruction of the bone marrow, spleen, lymph nodes and liver, with more cerebral form of infestation and the brain.In parenchymal organs is a high content of Gaucher cells, while existing areas of necrosis in the cerebral cortex diffuse changes occur.In a study of patients showed a sharp increase in the spleen and liver, and sometimes the lymph nodes.On the body there are characteristic for this disease spots dark yellow.
Gaucher disease has a characteristic symptom of the disease in the clinic as an increase in the spleen at the outset of developing pathology, and then an increase in size and liver.A certain pigmentation occurs on the face, hands, sclera and mucous membranes.A lipid accumulation in bone marrow leads to osteoporosis vertebrae, femoral bones to spontaneous fractures, anemia, thrombocytopenia and leukopenia.Sometimes even infants found a malignant form of the disease, which occurs in the form of spastic syndrome, strabismus, whooping cough.
In the acute form of Gaucher disease revealed hepatosplenomegaly with increased visceral lymph nodes.Open body takes pigment yellowish brown color, which later became the bronze-colored due to the postponement of a particular pigment under the skin.Patients typically complain of pain in the bones, deformation characteristic and frequent fractures.In old age, well traced severe symptoms atheromatosis vessels along with increased hypercholesterolemia.
At the last stage of Gaucher disease often develop severe forms of neurological disorders that lead to death.
Gaucher disease diagnosis
today to diagnose Gaucher disease using different methods.
One of the most accurate blood test is considered when determining the presence of the enzyme and the level of glucocerebrosidase in white blood cells.
In the analysis of DNA, the second method, consider the mutation at the genetic level and the number of missing the main enzyme.This method is based on the latest technologies of molecular biology.The main advantage of this diagnosis of Gaucher disease is that it allows the examination in early pregnancy.This allows up to 90% in the future, to determine a carrier of the disease and even its severity.
In the third method, the diagnosis investigate the bone marrow, which makes it possible to determine the dysfunction of its cells.The downside of this survey is that it only allows you to diagnose patients and to identify carriers of the disease, it can not.Therefore, as of today, this method is almost never used.
Unfortunately, sometimes the symptoms of Gaucher disease is not always easy.Therefore, it is correct and timely diagnosis can prolong the life of the patient for many years.At the same time the patient will be under the supervision of specialists (pediatricians, hematologists), without the use of medication and without fear of complications.Conversely, if a patient who has not passed in a timely manner qualified to diagnose and has not received medical treatment, may Lifelong have symptoms of the disease, suffer from them and had no idea that he had Gaucher disease, respectively, and did not receive proper treatment.
Gaucher disease treatment
More recently, the disease symptoms were treated by him: the spleen was removed and carried out the operation in pathological fractures.But in 1991, the United States has its first medication Aglyutseraza allowing to treat Gaucher's disease.This disease was first among storage diseases, which are susceptible to treatment with fermentozamenitelyami.
second product enzyme replacement therapy for Gaucher disease, imiglyutseraza, was officially adopted in 1994.These drugs are analogs of the human enzyme glucocerebrosidase, which are produced on the latest technologies of creating artificial DNA.
At the moment, all over the world a huge number of patients with Gaucher disease are constantly receiving treatment in the form of enzyme-modified forms of the beta-glucocerebrosidase.These include tseradaza (alglyutseraza) and Cerezyme (imiglyutseraza injection).These drugs are designed so that could specifically target the white blood cells (macrophages) that destroy infection to accelerate the degradation process glucocerebroside to glucose and ceramide.
documented success of the treatment of Gaucher disease using tserezima at an initial dose of 60 U per kg, which was applied every two weeks.After completing the course, registered what this dose significantly reduces organomegaly often reduces the internal organs in the size and complication of hematological etiology, and improves the lives of patients with the first type of Gaucher disease.
Since 1997, this pathological heredity treated with enzyme replacement therapy in Russia.For patients with a first type assignment Tserezima starts with 30 IU per kg once daily.Six months after the start of therapy Gaucher disease positive dynamics in many parenchymal organs, as well as hematological parameters.
Prolonged treatment of Gaucher disease with this drug is completely stabilizes the disease process, reduces the severity of changes in the bones and significantly improves the lives of patients.Therefore, the sooner appropriate treatment will be started, the more effective the results.
important point is to prevent Gaucher disease, which is to conduct genetic counseling of families and prenatal diagnosis.This makes it possible to identify the early stages of glucocerebrosidase activity still in the shell of the fetus and umbilical cord blood cells it.