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ENZYMOPATHIES AND DISTURBANCES OF MECHANISMS OF TRANSPORT OF NUTRIENTS ABETALIPOPROTEINEMIYA
This rather rare inborn disease inherited on autosomal recessively type is characterized by disturbance of absorption of fats, an acanthocytosis of erythrocytes, an ataxy and a pigmental degeneration of a retina. The etiology is completely not found out, however it is known that absence in intestines of lipoproteins of low density leads to disturbance of formation of normal chylomicrons, and also release and transport of triglycerides from cells of an intestinal epithelium. DEFICIT OF ENTEROKINASE
Clinical manifestations. Such patients are born healthy, but within the first year of life develop in a slowed-up way. Kal is decoloured, plentiful; the stomach will be stretched gases. At most of patients intellectual development is slowed also down. By 10 years signs of defeat of the central nervous system can be shown: the ataxy, lack of deep tendon jerks, proprioceptive and vibration sensitivity, a strong tremor reflecting changes in a cerebellum, back and lateral columns, peripheral nerves and basal gangliya. At teenagers the pigmental degeneration of a retina develops.
The diagnosis is made on the basis of detection in peripheral blood of acanthocytes, very low level of serumal cholesterol (0,2 — 0,8 g/l), absence or very small content of beta lipoproteins, characteristic accumulations of lipids in fleecy enterocytes of a duodenum (fig. 12-19, c). Usually at children of younger age the steatorrhea, but, except for absorption of fat and fat-soluble vitamins is observed, digestion of other nutrients is not broken.
Treatment. There is no specific treatment; high doses of fat-soluble vitamins (A, D, E y To) \Massive doses of vitamin E are appointed (100 mg/kg of body weight a day) can detain progressing of degenerative processes in a nervous system, Limiting receipt with food of the fats having a long chain it is possible to achieve weakening of intestinal symptoms; as replacement of the specified fats it is possible to use triglycerides with an average chain.
In literature children have few messages on cases of deficit of this enzyme of a small bowel. Enterokinase — the activator of trypsinogens of pancreatic juice therefore its deficit completely switches off proteolytic activity of a pancreas. At patients since the birth heavy diarrhea is observed, the arrest of development is noted. Often there is a hypoproteinemia which causes emergence of secondary hypostases. In duodenal juice activity of trypsin is absent while activity of amylase and a lipase is not changed. In vitro addition of enterokinase in duodenal juice recovers activity of trypsin. Thus, the leading sign of this state is disturbance of absorption of proteins; the easy steatorrhea is sometimes observed. Replacement therapy by pancreatic enzymes recovers digestive function. DISTURBANCES OF TRANSPORT OF AMINO ACIDS
Occur among inborn specific disturbances of an exchange of amino acids (chapter 8) - states which cornerstone defect of their transport in intestines is. Penetration of amino acids into a mucous membrane is complicated at a cystinuria, however such patients have no gastrointestinal symptoms. Malabsorption of tryptophane at Hartnup's illness causes an ataxy, mental retardation and pellagropodobny skin rash. Disturbance of absorption of methionine is followed by periodic ponosa, especially at blondes, a delay of mental development; urine of such patients contains a large number and - hydroxybutyric acid, has a sweetish smell. At a syndrome of blue diapers tryptophane absorption is broken. The child has a message on malabsorption of a lysine with a giperlizinuriya.
INSUFFICIENCY OF DISACCHARIDASES
Disaccharidases are localized on a surface of a brush border of an epithelium of a small bowel. The ratio between various enzymes changes in different terms of the prenatal and post-natal periods (see fig. 12-9). Insufficiency of disaccharidases sometimes happens inborn, but more often it arises for the second time owing to diffusion defeat of an epithelium of a gut, for example at an infection or a gluten illness. B12 VITAMIN ABSORPTION DISTURBANCE
Irrespective of the reason insufficiency of disaccharidases is shown equally — intolerance of disaccharides. Incomplete hydrolysis of disaccharides on a brush border leads to accumulation of sugar in a gut gleam. In distal part of a gut it is utilized by microflora therefore hydrogen and organic acids are formed. Sugar and organic acids detain water in a gut cavity, causing diarrhea; fecal masses foamy, friable; with low pH (less than 6,0), high content of sugar that causes excoriations on buttocks. The abdominal murmur and its swelling is noted; the steatorrhea happens seldom. At some children who were above early age, the leading place in clinic is taken not by(with) ponosa, but the abdominal pains caused by a meteorism.
If the patient does not transfer the reducing sugar, for example lactose, then in most cases standard "клинитест" shows + 1 or big sizes. Tests with loading various "suspected" sugars were applied to clinical diagnosis of intolerance of disaccharides, but they did not find a wide circulation. Activity of disaccharidases can be studied in bioptata of a mucous membrane. At children 4 years which can consciously follow instructions of the doctor are more senior, the intolerance of disaccharides can be revealed by determination of content of hydrogen in expired air after loading sugar.
Insufficiency of lactase. In literature some cases of inborn lack of lactase are described. Primary insufficiency of this enzyme is usually regarded as defect r and z in and t and I. The lactase activity arises during rather late period of pre-natal development and decreases to age of 3 years therefore the lactose intolerance can be shown at big prematurity, at children of advanced age or at adults. Weakening of a lactase activity in the childhood often occurs among representatives of negroid and Mongoloid race less often at Caucasians. As lactase contains in a mucous membrane in a small amount, its deficit especially easily arises as the secondary phenomenon at diffusion damages of intestines (section 12.58).
Clinical signs (diarrhea, abdominal pains) of insufficiency of lactase are observed after the use in food of the milk containing lactose, or milk sugar. Recently connect recurrent strong colicy pains in a stomach with this syndrome. At children of preschool and school age incidental pains in a mesogaster are possible. The general condition of the child at the same time does not suffer, accurate communication between attacks of pains and diarrhea, and also the milk use — with another, often is not traced (see also section 12.43).
Treatment consists in purpose of a nonmilk diet. In most cases it is enough to exclude only whole milk from food. Now there is a lactase drug which addition in milk allows to use it without any effects.
Insufficiency of invertase and isomaltase. The only inborn deficit of disakharidazny activity which is found quite often — the combined insufficiency of invertase and isomaltase. Symptoms usually arise at the use of food which contains sucrose. Also the intolerance of starch, but as isomaltase affects only starch molecule branching points is possible, the isolated insufficiency of this enzyme usually is shown by insignificant symptoms. The main symptoms — a foamy watery chair and excoriation of skin on buttocks. Recurrent abdominal pains at insufficiency of invertase and maltase are not observed. As sucrose belongs to not reducing sugars, it can be found by means of "klinitest" only after processing a calla hydrochloric acid. Morphologically small bowel is not changed; histochemical methods reveal deficit of invertase and isomaltase at the normal content of lactase and maltase. After loading sucrose the amount of hydrogen increases in expired air. The condition of patients quickly improves after reduction of content of sucrose in food to a minimum.
Malabsorption of glucose and galactose. This rare inborn disturbance of transport of glucose through a brush border is inherited on autosomal recessively type. In easy degree also the epithelium of renal tubules is surprised. Secondary disturbance of absorption of these sugars perhaps after acute viral enteritis or crushing chronic diffusion damage of a mucous membrane of a small bowel. If injury of a mucous membrane is so expressed that glucose absorption is broken, then absorption of other nutrients also suffers.
Clinical manifestations of disturbance of absorption of glucose are identical at the inborn and acquired defect. The liquid chair appears after the use of glucose, breast milk or artificial nutritious mixes as the majority of food sugars belongs to the polysaccharides or disaccharides containing glucose separately or with galactose impurity. The body weight of the patient can be increased, however at long diarrhea development of heavy dehydration and acidosis is possible. Fecal masses has acid reaction and contains sugar. Curves of portability of glucose and a galactose are flattened. Patients with an inborn form of a disease well transfer fructose as in other relations the structure and enzymatic activity of a small bowel are not broken.
Treatment consists in strict restriction of glucose and a galactose and the use of a fruktozosoderzhashchy diet. At more advanced age of the patient can acquire a small amount of glucose of a pla of sucrose.
Assimilation of B12 vitamin is broken at some rare inborn diseases. Insufficient development in a stomach of an internal factor is characteristic of juvenile pernicious anemia. Though the structure and function of a mucous membrane of a stomach in other relations remain normal, absorption of B12 vitamin is broken that conducts to megaloblastichesky anemia and a growth inhibition. INBORN MALABSORPTION OF FOLIC ACID
Lack of transcobalamine II — the protein which is carrying out vitamin transport through an intestinal wall belongs to hereditary states. It is shown by heavy megaloblastichesky anemia, diarrhea and vomiting.
Immerslund described other option of selective insufficiency of B12 vitamin at which its absorption in an ileal gut suffers. Other dysfunctions and a structure of an ileal gut at the same time are not revealed. By the end of the first year of life at the patient megaloblastichesky anemia which is often combined with a proteinuria develops.
Treatment consists in parenteral administration of vitamin on 1000 mkg a week at deficit of transcobalamine II and on 100 mkg a month in other cases.
Several cases of insufficiency of the folic acid caused by the isolated disturbance of its assimilation are described. At such children except megaloblastichesky anemia the cerebral degeneration develops. CHLORSCARCE DIARRHEA
This rare inborn syndrome consists in disturbance of transport chloride ions in an ileal gut. Surplus of hloridion in a cavity of a gut causes the heavy watery diarrhea Beginning right after the birth. Diarrhea has resistant character and leads to dehydration and sharp disturbance of balance of electrolytes — to a hypopotassemia, a hypochloridemia and an alkalosis that VITAMIN-D-ZAVISIMYY RICKETS
in general it is uncharacteristic for chronic diarrhea. Other mechanisms of intestinal absorption at the same time remain normal. Content of chlorides in Calais exceeds total quantity of ions of sodium and potassium. Adequate methods of treatment are absent. The diet enriched with potassium and containing few chlorides is recommended.
At this autosomal and recessive frustration disturbance of a metabolism of vitamin D causes calcium malabsorption. Other functions of intestines at this syndrome are not broken. PRIMARY HYPOMAGNESIEMIA
Disturbance of the mechanism of transport of magnesium conducts to a heavy hypomagnesiemia and a secondary gipokaltsiyemichesky tetany at children of younger age. Other functions of intestines are not changed. Symptoms of a disease disappear after introduction of high doses of magnesium; reception of magnesium it is necessary to continue vaguely long time. ENTEROPATICHESKY ACRODERMATITIS
Insufficiency of zinc owing to its malabsorption is the cornerstone of this unusual combination of clinical signs. Soon after the birth on border of skin and mucous membranes and on extremities rash develops. Besides, the alopecia, chronic diarrhea and sometimes a steatorrhea is observed. If treatment is not carried out, then the child lags behind in physical development. Concentration of zinc in blood serum is sharply reduced. In byoptata inclusions of cells of Panet which disappear after treatment are visible. Skin signs and diarrhea disappear after appointment in zinc heptahydrate sulfate in a dose of 150 mg/days. MENKES'S SYNDROME (SYNDROME OF CURLY HAIR)
Menkes's syndrome is inherited on recessive type, characterized by a growth inhibition, anomaly of a structure of hair, a cerebellum degeneration. Sick children die at early age. The pathogeny of an illness is not clear; it is known that copper transport through a cellular membrane both in intestines, and in other bodies is broken. Level of ceruloplasmin and copper in blood serum is reduced, but the content of copper in cells is increased. LEKARSTVENNOINDUTSIROVANNY DISTURBANCES OF ABSORPTION
Some drugs exert diffusion impact on an epithelium of a small bowel. For example, the methotrexate blocks mitoses in enterocytes, causing thereby damage of a mucous membrane;
Neomycinum in high doses also injures a mucous membrane. Sulfasalazinum influences absorption of folic acid. Connecting bile acids and calcium, holestiramin causes a hypocalcemia and a steatorrhea. Phenytoinum breaks calcium absorption that can become the rickets reason.