What is Anemia caused by a violation of the synthesis of porphyrin utilization?
Hereditary and acquired anemias are associated with impaired activity of enzymes involved in the synthesis of porphyrins and heme, hypochromic, with a high content of iron in the body and hemosiderosis of the organs. Hereditary anemias are relatively rare, mostly in men. Acquired forms are most often associated with intoxication. As a rule, lead poisoning and vitamin B6 deficiency are the causes of the acquired violation of porphyrin synthesis.
Hereditary violation of porphyrin synthesis occurs much more frequently in men, which is explained by inheritance linked to the X chromosome. In extremely rare cases, an autosomal recessive mode of inheritance is possible. However, this form of the disease is observed in women. In the majority of patients, the content of free protoporphyrin of erythrocytes is reduced, in some of them the content of coproporphyrin and porphyrin of erythrocytes is increased.
Pathogenesis during Anemias caused by impaired synthesis of porphyrin utilization
Violation of the synthesis of protoporphyrin characterizes the impossibility of binding iron and, as a result, its accumulation in the body. If iron comes predominantly to the liver, then cirrhosis occurs; with the deposition of iron in the pancreas develops diabetes.
The degree of clinical manifestations of the disease depends on the severity of anemia. Complaints are general in nature and usually boil down to weakness, fatigue. Since childhood, patients have moderate hypochromic anemia. Over the years, anemia deepens. There are clinical signs of excess iron deposits in the body. Severe muscle weakness may develop, diabetes mellitus signs are sometimes found, stomach pains and discomfort in the right hypochondrium periodically appear in some patients, shortness of breath, swelling in the legs, palpitations are possible.
An objective examination in some patients revealed a dark color of the skin, an enlarged liver, and sometimes a spleen.
Diagnosis of Anemias due to impaired synthesis of porphyrins
Anemia in adolescence in most cases is relatively small – hemoglobin is 80-90 g / l, but the hemoglobin content gradually decreases, reaching 40-60 g / l. The color index is usually sharply reduced – 0.4-0.6. The content of reticulocytes is usually normal or slightly reduced. The number of leukocytes, platelets, leukocyte formula are normal until then, until there are serious changes in the liver. In the bone marrow, there is a sharp irritation of the red sprout, an increase in the content of basophilic erythrokaryocytes and a decrease in hemoglobinized forms.
The serum iron content is quite strongly increased – 62.7-98.5 μmol / l (350-550 μg%). Transferrin saturation in most patients is almost 100%.
After intramuscular administration of 500 mg desferal in patients with impaired porphyrin synthesis, iron is excreted 5-10 mg / day. at a rate of 0.6-1.2 mg / day.
Sometimes an in vitro study of the biosynthesis of porphyrins from 6-aminolevulinic acid helps the diagnosis: 6-aminolevulinic acid is added to the patient’s erythrocytes, from which a large number of porphyrins form during 4 hours of shaking.
Differential diagnostics
Violation of the synthesis of porphyrins should be suspected in a situation where patients (mostly men) with hypochromic anemia have high levels of serum iron. Also in cases of hypochromic anemia there is a high serum iron content in thalassemia, and thalassemia is much more common than hereditary anemia associated with impaired porphyrin synthesis. In the same way as with thalassemia, with anemia associated with impaired porphyrin synthesis, signs of ineffective destruction of red blood cells and target-like red blood cells are found.
Thalassemia is more characteristic of an enlarged spleen. The serum iron content is, as a rule, lower than for anemia caused by impaired porphyrin synthesis.
The determination of the erythrocyte porphyrin content and the study of porphyrin biosynthesis in vitro (in vitro) from 6-aminolevulinic acid help the diagnosis. Thalassemia is inherited by the dominant type, namely heterozygous thalassemia is detected in different generations of the family.
A low color index with a high iron content is observed in case of acquired disorders in the synthesis of porphyrins, in particular in lead poisoning. Lead poisoning is manifested by basophilic erythrocyte punctures, target appearance, sideroblasts in the bone marrow with a circular arrangement of ferritin, which, as a rule, is also found in hereditary disorders of porphyrin synthesis. However, in lead poisoning there is damage to the nervous system, there are often abdominal pains, the spleen is not enlarged (sometimes it is enlarged in hereditary disorders of porphyrin synthesis). Of the biochemical signs in lead poisoning, there is an increase in the content of urine 6-aminolevulinic acid and coproporphyrin, in erythrocytes – an increase in the content of protoporphyrin.
Differential diagnosis is carried out with all diseases in which there is an excess of iron in the body. First of all, such diseases include hemochromatosis, which is a hereditary disease, in which a large excess of iron in the body is associated with a violation of the restriction of iron absorption from food. In hemochromatosis, patients do not have anemia. Hemoglobin formation in hemochromatosis is not disturbed. In the bone marrow there are no characteristic ring sideroblasts. A high iron content is found in diseases with decreased blood formation, for example, aplastic anemia and partial red-cell aplasia, in which there is no red germ of the blood. Due to a sharp decrease in the intensity of erythropoiesis in both diseases and due to frequent blood transfusions in the body, there is an excess of iron. It is deposited in all organs and causes hemosiderosis, similar to that in violation of the synthesis of porphyrins. They are distinguished from each other by a color index – it is normal for partial red-cell aplasia and aplastic anemia and is sharply reduced when violation of the synthesis of porphyrins. In the latter form, the content of peripheral blood reticulocytes is normal or slightly elevated, the content of bone marrow erythro-cryocytes is sharply elevated. With partial red-cell aplasia, the content of reticulocytes is sharply reduced, and the erythro-cryocytes in the bone marrow are extremely low.
For aplastic anemia, a sharp decrease in the level of platelets and neutrophils is typical, and a decrease in the number of megakaryocytes is observed in the bone marrow. In the study of bone marrow is determined by a large amount of fat.
The disease has to be differentiated from acquired dizerytropoeticheskoy anemia or, as it is often called, refractory sideroblastic anemia.
Common for both diseases are pronounced inefficient destruction of red blood cells, sharp irritation of the red bone marrow germ with a small amount of reticulocytes in the peripheral blood, a large number of sideroblasts, high serum iron and iron in the urine after administration of desferal, liver enlargement. Quite often, patients have an enlarged spleen. However, elderly people usually suffer from dizerythropoietic anemia, and young people usually suffer from hereditary anemia. The color index at a defect in the synthesis of porphyrins is sharply reduced, and in the diesi-tropoetic form it is close to the norm. The acquired form of the disease is accompanied by changes in white blood — a pronounced stab shift (up to 30–40%), often by peripheral monocyte. These changes are not in the hereditary form of the disease. In the case of a diteritropoietic form, the serum iron content is close to normal or unsharply increased, and in the hereditary form, a sharp increase in serum iron is noted. The hereditary form of the disease causes changes in the number of red blood cell porphyrins. With the acquired form, these changes are much smaller. Only in some patients the content of protoporphyrin in red blood cells is elevated.
Treatment of Anemia caused by impaired synthesis of porphyrin utilization
Treatment of hereditary anemia, resulting from a violation of the activity of enzymes involved in the formation of porphyrin proteins, must begin with vitamin B6. The goal of this therapy is to achieve sustained remission of the disease. In animals with vitamin B6 deficiency, in addition to dermatitis, glossitis and damage to the nervous system, hypochromic anemia develops with an increase in serum iron content and iron deposition in organs.
Not all patients with a hereditary violation of the synthesis of porphyrins are effective vitamin B6, almost half of it is useless. Doses of vitamin B6 for the treatment of this disease should be large (6% solution in a dose of 5-8 ml / day.). Pyridoxal phosphate is far superior in efficiency to vitamin B6. This drug is available in tablet form at a dosage of 20 mg, as well as in ampoules of 10 mg of the drug in solution. The dose of pyridoxal phosphate in the treatment of anemia is 30-40 mg / day. with intramuscular injection or 80-120 mg / day. when taken orally. The effect of the drug is observed faster than using vitamin B6.
To remove excess amount of iron from the body, it is necessary to apply desferal for 500 mg / day for a long time. It is advisable 3-6 times a year to conduct monthly courses of treatment with the specified drug. Sometimes the treatment with desferal leads to remission.
Forecast
The prognosis is satisfactory if it has the effect of vitamin B6 or pyridoxal phosphate and is used desferal, and much worse with late treatment and irreversible changes associated with organosis.