What is Hereditary Spherocytosis (Minkowski-Chauffard Disease)?
Hereditary spherocytosis (Minkowski-Chauffard disease) – hemolytic anemia due to a defect in the cell membrane of erythrocytes, the permeability of the membrane to sodium ions becomes excessive, and therefore the erythrocytes become spherical, become brittle and easily undergo spontaneous hemolysis.
Hereditary spherocytosis is a widespread disease (2–3 cases per 10,000 population) and occurs in individuals of most ethnic groups, but more often people in northern Europe are sick.
Causes of Hereditary Spherocytosis (Minkowski-Chauffard Disease)
Hereditary spherocytosis is transmitted in an autosomal dominant manner. As a rule, one of the parents exhibits signs of hemolytic anemia. Possible sporadic cases of the disease (in 25%), which are new mutations.
Pathogenesis during Hereditary Spherocytosis (Minkowski-Chauffard Disease)
In the pathogenesis of hereditary spherocytosis, two provisions are indisputable: the presence of a genetically determined anomaly of proteins, or spectrins, the erythrocyte membrane and the eliminating role of the spleen in relation to spheroidally modified cells. In all patients with hereditary spherocytosis, there is a deficiency of spectrins in the erythrocyte membrane (up to 1/3 of the norm), and in some of them a violation of their functional properties, and it has been established that the degree of deficiency of spectrin can correlate with the severity of the disease.
A hereditary defect in the structure of the erythrocyte membrane leads to its increased permeability to sodium ions and the accumulation of water, which in turn leads to an excessive metabolic load on the cell, loss of surface substances and the formation of spherocyte. Spherocytes forming when moving through the spleen begin to experience mechanical difficulty, lingering in the red pulp and being exposed to all kinds of adverse effects (hemoconcentration, pH change, active phagocytic system), i.e. the spleen actively damages spherocytes, causing even greater membrane fragmentation and spherulation. This is confirmed by electron microscopic studies, which allowed to detect ultrastructural changes in erythrocytes (thickening of the cell membrane with its ruptures and the formation of vacuoles). After 2-3 passages through the spleen, the spherocyte is subjected to lysis and phagocytosis. The spleen is the site of the death of red blood cells; life expectancy is reduced to 2 weeks.
Although the defects of erythrocytes in hereditary spherocytosis are genetically determined, conditions arise in the body under which these defects deepen and hemolytic crisis takes place. Crises can be triggered by infections, certain chemicals, and mental trauma.
Symptoms of Hereditary Spherocytosis (Minkowski-Chauffard Disease)
Hereditary spherocytosis can manifest itself from the neonatal period, but more pronounced symptoms are found by the end of preschool and early school age. Early manifestation of the disease determines a more severe course. Boys are sick more often.
Hereditary spherocytosis is hemolytic anemia with a predominantly intracellular type of hemolysis, which also causes clinical manifestations of the disease — jaundice, an enlarged spleen, a greater or lesser degree of anemia, and a tendency to form gallstones.
Complaints, clinical and laboratory symptoms are largely determined by the period of the disease. Outside hemolytic crisis complaints may be absent. With the development of hemolytic crisis, complaints of increased fatigue, lethargy, headache, dizziness, pallor, jaundice, loss of appetite, abdominal pain, fever to high numbers, nausea, vomiting, increased stools, a terrible symptom – the appearance of cramps.
Symptoms of a crisis is largely determined by anemia and depends on the degree of hemolysis.
An objective examination of the skin and visible mucous pale or lemon yellow. In children with early manifestations of hereditary spherocytosis, skeletal deformities are possible, especially the skull (tower, square skull, the arrangement of teeth, etc.); genetic stigmas are not uncommon. In patients with varying degrees of severity of changes in the cardiovascular system, due to anemia. Hepatolienal syndrome with a predominantly enlarged spleen is characteristic. The spleen is dense, smooth, often painful, which, apparently, is explained by the stress of the capsule due to blood filling or perisplenitis. The color of excrement at the time of the crisis is intense. Possible fluctuations in the size of the spleen should be noted: a significant increase in hemolytic crises and a decrease in the period of relative well-being.
Depending on the severity of hereditary spherocytosis, clinical symptoms may be mild. Sometimes jaundice can be the only symptom about which the patient sees a doctor. It is to these persons that Chauffard’s famous expression applies: “They are more jaundiced than sick.” Along with the typical classical signs of the disease, forms of hereditary spherocytosis are encountered, when hemolytic anemia can be so well compensated that the patient learns about the disease only with the appropriate examination.
Along with the most typical hemolytic crises in severe hereditary spherocytosis, regenerative crises are possible with symptoms of hypoplasia of predominantly the red bone marrow germ. Such crises can develop acutely with fairly vivid symptoms of anemia-hypoxia and are usually observed in children after 3 years of life. Regenerative crises are short-term (1-2 weeks) and are reversible, unlike true aplasia.
Hereditary spherocytosis is complicated by the formation of pigment stones in the gallbladder and bile ducts; after 10 years, gallbladder stones are found in half of the patients who have not undergone splenectomy.
Diagnosis of Hereditary Spherocytosis (Minkowski-Chauffard Disease)
The diagnosis of hereditary spherocytosis is made on the basis of the genealogical history, clinical data described above and laboratory studies. The hemolytic nature of anemia is confirmed by normochromic normocytic anemia with reticulocytosis, indirect hyperbilirubinnemia, the severity of which depends on the severity of hemolysis. The final diagnosis is based on the morphological features of erythrocytes and the characteristic feature of hereditary spherocytosis – a change in the osmotic resistance of erythrocytes.
The morphological features of erythrocytes in hereditary spherocytosis include a spherical shape (spherocytes), a decrease in diameter (average erythrocyte diameter <6.4 μm), an increase in thickness (2.5-3 μm at a rate of 1.9-2.1 μm) and usually normal average red blood cell volume. The hemoglobin content in erythrocytes within the physiological norm or slightly higher. CPU close to 1.0. Price-Jones erythrocytometric curve is stretched, rolled to the left. The leukogram changes only during the crisis (leukocytosis with neutrophilia, the shift of the leukocyte formula to the left), the ESR during the crisis is increased. Platelet count is normal.
A characteristic feature of hereditary spherocytosis is a decrease in the minimum osmotic resistance (persistence) of erythrocytes – hemolysis begins with 0.6-0.7% NaCl (norm 0.44-0.48% NaCl). To confirm the diagnosis, it is important to significantly lower the minimum osmotic resistance. Maximum resistance can be increased (the norm is 0.28-0.3% NaCl). Among patients with hereditary spherocytosis, there are those who, despite obvious spherocytosis, under normal conditions, osmotic stability of erythrocytes is normal. In these cases, it is necessary to investigate it after the preliminary daily incubation of red blood cells.
The course of hereditary spherocytosis is undulating. Following the development of the crisis, clinical and laboratory parameters are improving and remission is occurring, which can last from several weeks to several years.
Differential diagnosis. Hereditary spherocytosis should be differentiated from other congenital hemolytic anemias. Family history data, a study of blood smears and osmotic resistance of erythrocytes are of the greatest diagnostic value.
Of the other diseases, hereditary spherocytosis is primarily differentiated from hemolytic disease of the newborn, and at an older age with viral hepatitis, autoimmune hemolytic anemia.
Treatment of Hereditary Spherocytosis (Minkowski-Chauffard Disease)
Treatment of hereditary spherocytosis is carried out depending on the clinical manifestations of the disease and the age of the child. In the period of hemolytic crisis treatment is conservative. The patient is hospitalized. The main pathological syndromes that develop during the crisis period are: anemia-hypoxia, cerebral edema, hyperbilirubinemia, hemodynamic disorders, acidotic and hypoglycemic changes. Therapy should be aimed at eliminating these disorders according to generally accepted regimens. Erythromass transfusions are indicated only with the development of severe anemia (8-10 ml / kg). The use of glucocorticoids is impractical. On exit from the crisis, the regime is expanded, the diet, cholagogue drugs are prescribed (mainly cholekinetics). In the case of the development of areregenerative crisis, replacement transfusion therapy and stimulation of hemopoiesis (erythromass transfusion, prednisolone 1-2 mg / kg / day, Vit. B12 until reticulocytosis, etc.) is necessary.
A radical method of treatment of hereditary spherocytosis is splenectomy, which provides practical recovery, despite the safety of spherocytes and a decrease in osmotic resistance (their severity decreases). The optimal age for surgery is 5-6 years. However, age cannot be considered as a contraindication to surgical treatment. Severe hemolytic crises, their continuous flow, regenerative crises are indications for splenectomy, even in young children. There is an increased tendency to infectious diseases within 1 year after surgery. In this regard, in a number of countries, monthly introduction of bicillin is taken within one year after splenectomy, or before planned splenectomy, pneumococcal polyvaccine is immunized.
The prognosis for hereditary spherocytosis is favorable. However, in severe cases of hemolytic crisis with delayed treatment is serious (possible fatal outcome).
Since hereditary spherocytosis is inherited in an autosomal dominant type with a rather high penetrance of the gene, it is necessary to take into account that the risk of having a sick child (of either sex) in the presence of hereditary spherocytosis in one parent is 50%. Children with hereditary spherocytosis are on a regular check-up.
Diet. Introduction to the diet of increased amounts of folic acid (more than 200 µg / day). Recommended products: baked goods from wholemeal flour, buckwheat and oatmeal, millet, soybeans, beans, chopped raw vegetables (cauliflower, green onions, carrots), mushrooms, beef liver, cottage cheese, cheese.
Prevention of Hereditary Spherocytosis (Minkowski-Chauffard Disease)
Hereditary spherocytosis cannot be prevented. However, people with hereditary spherocytosis may turn to a genetic counselor in order to discuss the possibility of identifying a defective gene that causes the disease of their children.
Prevention of hereditary spherocytosis is reduced to therapeutic measures during crises.