Disease Minkowski-Shoffara (spherocytosis)

Description:

The hereditary spherocytosis (Minkowski-Shoffara's disease) is a hemolitic anemia which cornerstone structural or functional disturbances of membrane proteins are, proceeding with an intracellular hemolysis.
The German therapist O. Minkowski (1900) gave the first the description of family hemolitic anemia; M. A. Shoffar (1907), the French therapist, found decrease in resistance of erythrocytes and the hemolysis strengthening connected with it in patients.
The disease is widespread everywhere, the frequency of occurrence makes 1:5 000 in population. It is transferred on autosomal dominantly type; about 25% of cases sporadic, caused by emergence of a new mutation.
Meets more often at inhabitants of Northern Europe where prevalence of a disease makes 1 on the 5000th population.
The autosomal and dominant mode of inheritance meets approximately in 75% of cases. Members of the family of the patient have a weight of anemia and degree of a spherocytosis can vary. In 25% of cases the family anamnesis is absent. At a part of patients of change of laboratory indicators are minimum that assumes an autosomal and recessive mode of inheritance, other cases - result of natural mutations.

Etiologies of Minkowski-Shoffara (spherocytosis):

The hereditary spherocytosis is transferred on autosomal dominantly type. As a rule, at one of parents reveal symptoms of hemolitic anemia. The sporadic cases (in 25%) representing new mutations are possible.

Pathogeny:

In a pathogeny of a hereditary spherocytosis 2 provisions are indisputable: existence of genetically determined anomaly of proteins, or spectrins, membranes of erythrocytes and an eliminiruyushchy role of a spleen concerning sferoidalnoizmenenny cells. At all patients with a hereditary spherocytosis deficit of spectrins in an erythrocyte membrane (to 1/3 norms), and at some - disturbance of their functional properties is noted, and it is established that degree of deficit of spectrin can correlate with disease severity.

Hereditary defect of structure of a membrane of erythrocytes leads to a hyperpermeability it for ions of sodium and to water accumulation that in turn conducts to excessive metabolic load of a cell, loss of surface substances and formation of a sferotsit. The forming sferotsita at the movement through a spleen begin to experience mechanical difficulty, being late in a red pulp and being exposed to all types of adverse effects (haemo concentration, change рН, active phagocytal system), i.e. the spleen actively puts to damage sferotsita, causing still big fragmentation of a membrane and a sferulyation. It is confirmed at the electronic microscopic examinations which allowed to find ultrastructural changes in erythrocytes (a thickening of a cellular membrane with its gaps and vacuolation). Through 2-3 passages through a spleen sferotsit is exposed to lysis and phagocytosis. The spleen is the place of death of erythrocytes; which life expectancy is reduced to 2 weeks.
Though defects of erythrocytes at a hereditary spherocytosis are caused genetically, in an organism there are conditions under which these defects go deep and hemolitic crisis is implemented. Crises can be provoked by infections, some chemicals, mental injuries.

Symptoms of a disease of Minkowski-Shoffara (spherocytosis):

Weight and a variety of a clinical picture are caused by a type of the structural protein which is absent on an erythrocyte membrane (insufficiency and - chains of spectrin is inherited autosomal it is prepotent and proceeds easily, and insufficiency of a beta chain causes the serious illness inherited autosomal рецессивно). In half of cases the hereditary spherocytosis is shown already in the neonatality period, imitating a picture of a hemolitic disease of newborns or a long pairing hyperbilirubinemia. The clinical picture of hemolitic crisis consists of a triad of symptoms: pallor, jaundice, splenomegaly. Crises can be provoked by infectious diseases, reception of a number of medicines, but can be spontaneous. Patients do not complain to the mezhkrizovy period, but the increased spleen at them is palpated always. The heavier the disease proceeds, the certain fendtipichesky features are expressed more clearly, namely: a tower skull, the Gothic sky, a wide nose bridge, long distances between teeth. These changes of a bone tissue are connected with a compensatory hyperplasia of marrow (an erythroidal sprout), and, as a result, osteoporosis of flat bones. Depending on weight of a hereditary spherocytosis degree of manifestation of clinical symptoms can be various. Jaundice can sometimes be the only symptom concerning which the patient sees a doctor. The known expression of M. A. Shoffar concerns to these persons: "They are more zheltushna, than are sick". Along with typical classical symptoms of a disease forms of a hereditary spherocytosis when hemolitic anemia can be so well compensated that the patient learns about a disease only when carrying out the corresponding inspection meet.

Diagnosis:

The diagnosis is confirmed by the family anamnesis and a number of laboratory researches.
Datas of laboratory
In a gemogramma normokhromny hyper regenerator anemia of various degree of manifestation is found. The maintenance of reticulocytes depends on weight of anemia and the period of a disease and fluctuates from 50-60 to 500-600%; there can be normocytes. At a morphological research of a smear of red blood find characteristic morphological features: along with normal erythrocytes there are microspherocytes - the small, intensively painted cells without the central enlightenment, characteristic of normal erythrocytes. The quantity of microspherocytes can fluctuate ranging from 5-10% to absolute majority. It is established that the more quantity of microspherocytes, the more intensively hemolysis. In the period of hemolitic crisis the leukocytosis with neutrophylic shift, acceleration of SOE can be noted.
The indirect hyperbilirubinemia which degree depends on weight of hemolitic crisis is biochemical observed. Level of a gaptoglobin decreases.
In sternal punctate there is a hyperplasia of an erythroidal sprout, the leykoeritroblastnchesky ratio is reduced to 1:2, 1:3 (against 4:1 is normal) at the expense of cells of an erythroidal sprout.
After the patient's exit from hemolitic crisis in the period of compensation of hemolysis for confirmation of the diagnosis carry out an eritrotsitometriya with curve Price's creation - Jones and define osmotic resistance of erythrocytes. Reduction of diameter of erythrocytes - the average diameter of erythrocytes less than 6,4 microns (diameter of normal erythrocytes of 7,2-7,9 microns) and shift of an erythrocytometric Price-Jones curve is characteristic of patients with a hereditary microspherocytosis to the left. A pathognomonic sign is change of osmotic resistance of erythrocytes. Normal indicators make: for the minimum resistance (the beginning of hemolysis) in 0,44% NaCl solution and for maximum (full hemolysis) - in 0,32-0,36% NaCl solution. Decrease in the minimum resistance of erythrocytes is typical for a disease, that is hemolysis begins in 0,6-0,65% NaCl solution. The maximum osmotic resistance can be even a little raised - in 0,3-0,25% NaCl solution.

Treatment of a disease of Minkowski-Shoffara (spherocytosis):

Treatment of a hereditary spherocytosis is carried out depending on clinical displays of a disease and age of the child. In the period of hemolitic crisis treatment conservative. The patient is subject to hospitalization. The main pathological syndromes developing in the crisis period are: anemia hypoxia, brain hypostasis, hyperbilirubinemia, hemodynamic disturbances, atsidotichesky and hypoglycemic shifts. Therapy has to be directed to elimination of these disturbances according to the standard schemes. Transfusions of erythroweight are shown only at development of heavy anemia (8-10 ml/kg). Use of glucocorticoids is inexpedient. On an exit from crisis the mode, a diet extends, cholagogue drugs are appointed (preferential holekinetik). In case of development of aregeneratorny crisis replacement hemotransfusionic therapy and stimulation of a hemogenesis is necessary (erythroweight transfusions, Prednisolonum of 1-2 mg/kg/days, Vit. B12 before emergence of a reticulocytosis, etc.).

Radical method of treatment of a hereditary spherocytosis is the splenectomy which provides practical recovery, despite safety of sferotsit and decrease in osmotic resistance (degree of their expressiveness decreases). Optimum age for carrying out operation of 5-6 years. However the age cannot be considered as a contraindication to surgical treatment. Heavy hemolitic crises, their continuous current, aregeneratorny crises - indications for carrying out a splenectomy even at children of early age. There is an increased tendency to infectious diseases during 1 year after operation. In this regard in a number of the countries monthly introduction within one year after Bicillinum splenectomy - 5 is accepted or before a planned splenectomy carry out immunization by a pneumococcal polyvalent vaccine.

The forecast at a hereditary spherocytosis favorable. However, in hard cases of hemolitic crisis at untimely treatment is serious (the lethal outcome is possible).

As the hereditary spherocytosis is inherited on autosomal dominantly type with quite high penetrance of a gene, it is necessary to consider that the risk degree of the birth of the sick child (any floor) in the presence of a hereditary spherocytosis at one of parents makes 50%. The children sick with a hereditary spherocytosis are on the constant dispensary account.

Diet. Introduction to a diet of the increased amount of folic acid (more than 200 mkg/days). The recommended products: bakery products from coarse flour, buckwheat and oat grain, millet, soy, haricot, the crushed crude vegetables (a cauliflower, green onions, carrots), mushrooms, beef liver, cottage cheese, cheese.

Prevention:

Hereditary spherocytosis it is impossible to warn. However the people sick with a hereditary spherocytosis can address the consultant geneticist to discuss possibilities of definition of a defective gene, vyzyvayukshchy a disease of their children.

Prevention of a hereditary spherocytosis comes down to medical actions during crises.