Beginning >> Articles >> Archives >> Practical hematology of children's age

Accumulation diseases - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Remission and recurrence of an acute leukosis
Inborn leukosis
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

Chapter VI
Diseases of accumulation represent big group of hereditary pathology which cornerstone defects of the enzymatic systems which are taking part in lipidic, carbohydrate, proteinaceous exchanges are. Allocation of such group of diseases is conditional as at the modern level there is an accurate pathogenetic classification. Disturbance of fermental systems leads to accumulation of the corresponding specific metabolites in macrophagic elements with the subsequent infiltration of bodies and body tissues. For accumulation diseases typical clinical symptoms are defeat of the central nervous system, muscular system, bone disturbances, increase in a liver and spleen. Clinical symptoms are caused by preferential accumulation of pathological material in this or that body. Traditionally some diseases from this group (an illness to Gosha, Nimann's illness — Peak) carry to hematologic pathology as they are followed by changes of blood and marrow. Such patients are treated in specialized hematologic hospitals, at the same time an illness Thea — Saks from the same group, but with the leading defeat of the central nervous system, it is considered destiny of psychoneurologists. In certain cases hematologic changes are expressed by emergence of abnormal cells as, for example, Alder's anomaly at mukopolisakharidoza.


Most often from diseases of accumulation in clinical practice the illness to Gosha meets. The disease is for the first time described by P. E. Gaucher in 1882. It belongs to enzymopathies of a lipidic exchange, sphingolipidoses at which there is a glucocerebroside accumulation. In 1965 R. The lake of Brady and coauthors established that the main disturbances are available at the first stage of utilization of glucocerebroside, the glyukotserebrozidaza caused by deficit. Activity of enzyme at a chronic form of an illness to Gosha is reduced by 65%, and at acute — is practically absent, in comparison with healthy people. The heaviest changes are observed in a spleen where the content of glucocerebroside in several cells times more normal concentration. Pathological substrate is laid in lymph nodes, a liver, marrow, tubular bones, fabric of a nervous system. The preferential infiltration glucocerebroside of a spleen is caused by the fact that it is a component of a stroma of eeritrotsit which generally collapse in a spleen. Pathological substrate of a disease is provided by cells to Gosha - it is large cells with a peculiar morphology. The size varies them from 20 to 40 microns, an ovate-orbicular configuration and with excentricly located small kernel. Except one-nuclear, meet two - and three-nuclear cells to Gosha. Kernels have a dense net, the roundish, sometimes a little wrinkled form. Nukleola in a kernel are not defined. The structure of cytoplasm is characteristic: when coloring across Romanovsky cytoplasm has a layered and cellular structure and occupies the most part of a cell, is painted in pink color. The layered structure is caused by existence tyazhy, surrounding all cytoplasm. At elektronnomikroskopichesky research they are presented in the form of the double chains formed by glucocerebroside molecules. Among cells Gosha can meet also forms without inclusions which cytoplasm is painted in bluish color. It is connected with various phases of development of macrophagic elements. Sometimes find the cells with a foamy structure of cytoplasm reminding Nimann's cells — Peak, however cytochemical changes testify to their belonging to cells to Gosha. Tsitokhimicheski note the expressed reaction to acid phosphatase, CHIC reaction, weak coloring on and-naftilatsetat esterase, sudanophil granules reveal. N. S. Kislyak and R. V. Lenskaya (1978) note that reaction with Sudan III on neutral fats is indicative. Cells to Gosha are painted in yellowish-orange color that distinguishes them from other cells giving light yellow coloring
The most expressed histologic changes define in a spleen. The spleen reaches the huge sizes. On cuts the pulp has "marble" drawing — a set of the yellowish specks formed by accumulation of cells to Gosha. Similar infiltrates find in a liver which considerably increases and loses lobular structure. In a bone tissue the focal defeats with development of destruction of a bone which are combined with sclerous changes are observed. Mainly process affects big bones — tibial, femoral, humeral. Adjournment of pathological substrate happens in lymph nodes that conducts to their moderate hyperplasia. Also deposits in skin with coloring change, especially in the places which are treated to action of light are noted. Pathological changes find in an eye cornea. In marrow, unlike a spleen, cells to Gosha are disseminated among normal haemocytes, at a large number meet on two-three at once. Specific deposits are noted also in lungs, there is an infiltration alveolar macrophages of intersticial pulmonary fabric. At a chronic form of an illness to Gosha the circle of the struck bodies is usually limited to the hemopoietic, lymphatic and bone systems. At an acute form considerable accumulation of glucocerebroside in a nervous system is noted, organs of sight, a digestive tract, adrenal glands, kidneys are also surprised. In a nervous system there are big accumulations of cells around vessels, in neurons. The degeneration of neurons of a thalamus, basal gangliyev kernels of a trunk, a spinal cord and cerebellum develops.
The illness to Gosha has family character, quite often in one family brothers and sisters can be ill. The disease with an identical frequency occurs at persons man's and female. It is transferred on autosomal recessively type which is not linked to a floor. At persons with a heterozygous carriage of a pathological gene activity of glucocerebroside in leukocytes is reduced. It is supposed that pronichesky and acute forms of an illness to Gosha are caused by two various allelic recessive mutations of an autosomal gene. In literature there are descriptions of cases where it is about a dominant mode of inheritance with an incomplete penetratnost that is noted in the closed ethnic groups.
Weight of clinical signs at an illness to Gosha is in direct dependence on degree of enzymatic defect. What activity of enzyme is more reduced, that at earlier age and in more severe form shows a disease. Allocate three forms of an illness to Gosha: infantile — arises at children of chest age, juvenile — it is noted at children of younger and middle age and so-called adult — occurs at children of advanced age and adults. Depending on a clinical current distinguish: 1) the acute children's option arising at infantile and early juvenile forms and which is characterized by quickly progressing current with the expressed neurologic disturbances; 2) chronic — is observed at adults and at late juvenile forms. The disease differs in a long current which leading syndrome is the splenomsgaliya.
The acute malignant current is noted when developing a disease at chest age. Children are born externally healthy. Soon the child has lag signs in psychomotor development. The bad increase in the weight and growth is noted. There is no adequate will increase reaction on surrounding, children sluggish, apathetic. Gradually the hypotrophy forms. The acute current is characterized by generalized damage of internals that defines a variety of clinical symptoms. Quickly increases in the amount of a stomach in connection with a gepatosplenomegaliya. Various neurotic disturbances — a delay in psychoneurological development, attacks of tonikoklonichesky spasms, an opisthotonos are characteristic. Bulbar frustration are characterized by silent shout of the child, defeat of third cranial nerves in the form of the meeting squint, swallowing disturbance. The muscular hypertension — a stiff neck, the bent, not becoming straight extremities develops; spastic rigidity can reach full decerebration. Moderately lymph nodes increase. Specific damage of lungs leads to development of respiratory frustration. There is cough, cyanosis, short wind, respiratory insufficiency progresses. In blood anemia and thrombocytopenia accrue, the hemorrhagic syndrome develops. In marrow the considerable infiltration by cells to Gosha is noted. The forecast at chest age adverse. Disturbance of swallowing leads to impossibility of meal, heavy dystrophy, decrease in reactivity of an organism. The death occurs from accession of secondary complications — pneumonia, respiratory frustration, aspiration of food masses. The lethal outcome is observed on the first year of life. The acute current is noted also at a juvenile form of an illness to Gosha at children of preschool and younger school age. Process is also characterized by considerable generalization, damage of various internals, infiltratsiy marrow, but proceeds less violently. The death occurs at the phenomena of dystrophy and heavy neurologic frustration. Duration of a disease does not exceed 2 years from the moment of emergence of the first clinical symptoms. In blood — the expressed anemia and thrombocytopenia. Specific cells to Gosha in blood are not found as they do not eliminirut from marrow.
The clinical option of an illness to Gosha which is characterized by a chronic current is more high-quality form. The disease can also arise at children's age and long time to proceed asymptomatically. The first signs appear at youthful age or at adults. Due to the long asymptomatic initial stage even anamnesticly it is difficult to determine the moment of developing of a disease. The first symptoms are, as a rule, caused by damage of a spleen — there are unsharp pain in left a hypochondrium, feeling of completeness in this area. Then moderate increase in a spleen and liver is noted. At children the option of an onset of the illness to Gosha from defeat of bone system is described. In a clinical picture the ostealgia of the lower extremities, lameness dominated. At a chronic current the nervous system is, as a rule, not struck and lag in psychophysical development is not observed. Generally there is an infiltration of bodies of an optional hemopoiesis (a spleen, a liver), a bone tissue and marrow. The leading clinical symptom — a splenomegaly. The spleen can reach the huge sizes and be defined at an entrance to a small pelvis. It is dense, hilly, because of existence of an episplenitis can be painful. A bit later the liver which can also reach the big sizes, at a palpation dense, painless is involved in process. Jaundice and ascites are not characteristic of an illness to Gosha. The expressed gepatosplenomegaliya leads to significant increase in volume of a stomach. Patients have a characteristic appearance — the big sticking-out stomach. Often bone changes develop, tubular bone pain — femoral, humeral disturbs. Because of a megalgia mobility is limited. Spontaneous fractures of long tubular bones, deformation of a skeleton, formation of a hump, development of osteomyelitis are possible. At X-ray inspection define osteoporosis and cysts of bones, expansion of the marrowy channel and an atrophy of a cortical layer of tubular bones. Characteristic radiological features reveal in femoral and tibial bones. Owing to a hyperostosis symmetrically on both sides a diaphysis of a bone has club-shaped deformation — "Erlenmeyer's flask". Skull bones usually do not suffer. At an illness to Gosha skin changes in a type of sites of yellowy-brown pigmentation, with preferential localization on a back, hands are observed, but, as a rule, they arise during the late period. Similar changes can be on mucous membranes. Maculas lutea meet also on folds. The hyperadenosis — rather rare symptom also has moderate character. The picture of blood has no specific characters. The moderate anemia, a leukopenia, thrombocytopenia accruing during the terminal period are noted. On the one hand, the pancytopenia is caused by a marrow infiltration cells to Gosha, with another — a hypersplenism. The hemorrhagic syndrome a long time has moderate character in the form of hypodermic hemorrhages, nasal, gastro intestinal bleedings join later. It is caused both by progressing thrombocytopenia and development of the portal hypertensia which is followed by a varicosity of a digestive tract. In a leykogramma are possible a moderate neutropenia with a lymphocytosis and a monocytosis. Cells to Gosha in peripheral blood do not meet. They are found at research of a miyelogramma.
The general condition of patients can remain satisfactory. The general weakness, fatigue, subfebrile temperature are noted. Long time remains working capacity. At a chronic form the disease shares many years. It is noted that the disease has especially a long current, than at more advanced age its first signs appeared. Many children live up to adult age. Despite rather high-quality current, the forecast remains adverse. At patients the cachexia develops, heavy consecutive infections, hemorrhages in vitals are observed that as a result leads to a lethal outcome.
The main criterion of diagnosis of an illness is detection of cells to Gosha in a miyelogramma and punctates of a spleen. At children's age diagnosis can be difficult as the leader to a simptomokompleka — a splenomegaly, anemia, thrombocytopenia, a leukopenia — is observed also at other diseases. In this regard the splenomegaly of not clear origin serves as the indication for a diagnostic puncture of a spleen. Now possibilities of diagnosis of an illness to Gosha extended. Biochemical researches allow to define low activity of enzyme of a glyukotserebrozidaza in leukocytes of peripheral blood, culture of skin fibroblasts, fabric homogenates. Statement of the diagnosis is possible during the prenatal period. Chemical determination of the increased content of glucocerebroside in biopsy material and an urocheras is a diagnostic character. Increase of activity of acid phosphatase is characteristic. At a blood analysis the level of serumal lipids is in limits of normal amounts. Some increase in glucocerebroside fraction of phospholipids is noted. Cholesterol level in plasma normal. Crude protein and protein fractions have also no special aberrations. In respect of differential diagnosis it is necessary to exclude Nimann's illness — Peak and other diseases of accumulation, hemolitic processes.
Treatment of an illness to Gosha symptomatic — fight against consecutive infection, transfusions of components of blood. At a chronic current a palliative measure is the splenectomy, it considerably reduces a cytopenia and a hemorrhagic syndrome. Recently perspectives in treatment connect with replacement therapy — administration of missing enzyme, the purified enzymatic drugs.

"Workshop on nervous diseases and neurosurgery   Practical training on pharmaceutical technology of drugs"