The group of hereditary diseases which cornerstone the disturbances of a porphyrinic exchange leading to increase in contents in an organism of porphyrines or their predecessors are treats porphyrias. Porphyrines are synthesized in all cells of an organism, mainly in marrow and a liver in which they are used for formation of hemoglobin and enzymes (tsitokhrom, a catalase, peroxidase and others).
Epidemiology Data on prevalence of various forms of porphyrias are absent. There are only data on the variyegatny porphyria which is found most often at persons of white race of South Africa, descendants of immigrants from Holland. Patients with this form of porphyrias are found in Finland.
Etiology and pathogeny Modes of inheritance and pathogenetic features of various forms of erythropoietic and hepatic porphyrias are given at the description of each of them separately.
Classification Distinguish an erythropoietic uroporfiriya and an erythropoietic protoporphyria from erythropoietic porphyrias. Among hepatic — the acute alternating porphyria, a hereditary koproporfiriya, a variyegatny porphyria, an urokoproporfiriya.
Clinic The erythropoietic uroporfiriya — a rare inborn serious illness, is inherited autosomno on recessive type, observed in one generation sometimes at several children, at parents — heterozygous carriers of a pathological gene — clinical displays of an illness are absent.
The disease can be shown at newborns, there is an urine of red color, a photosensitization (the uroporphyrinogen which is released from erythrocytes is oxidized in uroporfirin and it is postponed in skin), several weeks later or months after the birth on a body of the child there are bubbles with the subsequent development of ulcers which against an antibioticotherapia cicatrize, leaving sites of the sclerosed face skin and other localization. The child quite often has a contracture of joints and a blindness, there are no hair, nails.
Increase in a spleen is found in patients. Hemolitic anemia with an intracellular hemolysis comes to light, the level of free bilirubin of blood serum and the maintenance of reticulocytes is increased, the erythro-normoblastic sprout in marrow is expanded. The prodozhitelnost of life of erythrocytes is shortened, their osmotic resistance is often reduced. Also coproporphyrin of urine and erythrocytes is raised uroporfirin. The disease results in disability and is frequent to death at early children's age.
The erythropoietic protoporphyria arises in the childhood, autosomal is inherited it is prepotent, in a pathogeny — the synthesis disturbance gem from protoporphyrin concerning, apparently, part of eritrokariotsit and also is possible increase in synthesis and - aminolevulinic acid. At patients the expressed increase of sensitivity to solar radiation is noted (the cutaneous dropsy, an itch, reddening, on places of burns arise bubbles with the subsequent ulceration). In most cases the disease proceeds not so hard as an erythropoietic uroporfiriya. Hems usually are not formed. The maintenance of an uroporfirin and coproporphyrin in erythrocytes and in urine is more often normal, protoporphyrin IX in erythrocytes — is increased. Protoporphyrin level in a blood plasma can be also increased. To Ania-mization owing to hemolysis develops seldom that is caused by existence of two populations of predecessors of erythrocytes in marrow (which are not changed and containing considerably the increased amount of protoporphyrin). Sometimes there are hemorrhages connected with deposits of a hyalin in walls of vessels and the subsequent their gap. The spleen increases seldom.
The erythropoietic koproporfiriya represents extremely rare disease, autosomal is inherited it is prepotent, reminds an erythropoietic protoporphyria on a clinical picture. Content of coproporphyrin increases in erythrocytes by 30 — 80 times in comparison with norm, excretion of large amounts of coproporphyrin III with urine and a stake is observed. The photosensitization is expressed unsharply. The bad attack of an illness can be provoked by reception of barbiturates.
The acute alternating porphyria — one of forms of hepatic porphyrias received such name because though the characteristic heavy neurologic phenomena can lead to death, but sometimes they abate and there is a remission. The disease is inherited autosomal is prepotent, its pathogeny is connected with disturbance of activity of enzyme uroporphyrinogen-1-sintetazy and increase of activity of a sintetaza delta aminoleaulinovoy the acid exerting toxic impact on a nervous cell.
Content of porphyrines in erythrocytes normal. In urine the increased quantity of an uroporfirin of I and II, and also coproporphyrin III is found. In perirod process aggravations in urine the predecessor of porphyrines — porphobilinogen comes to light. Level of a hepatic sintetaza, delta and aminolevulinic acid is increased. Urine porphobilinogen is considerably raised.
Approximate formulation of the diagnosis: 1. The erythropoietic uroporfiriya proceeding with a fotosesibilization (emergence of a pas a body of bubbles with the subsequent development of ulcers and their scarring), the intracellular hemolysis of erythrocytes raised by the level of free bilirubin of blood serum, a reticulocytosis and an expanded erythrogenesis in marrow. 2. The acute alternating hepatic porphyria with an abdominal pain syndrome, a polyneuritis, respiratory paralyzes, a cachexia.
The most frequent symptoms are abdominal pains of various localization that quite often leads to surgical intervention, heavy polyneurites, paresthesias, psychoses and comas, increase of arterial pressure and release of pink urine are observed. The lethal outcome is usually caused by respiratory paralyzes, some patients perish in the period of a coma or from a cachexia. The exacerbation of a disease is often provoked by pregnancy, reception of medicines (barbiturates, streptocides, analginum). At relatives of patients biochemical symptoms of an illness in the absence of any clinical symptoms (a latent form of the alternating porphyria) can come to light.
The hereditary koproporfiriya is inherited on autosomal dominantly type, often proceeds latentno. At this illness disturbance of activity of enzyme of a koproporfirinogenoksidaza, increase of synthesis of delta and aminolevulinic acid in a liver is found. On clinical manifestations reminds the acute alternating porphyria. In urine in the period of an exacerbation of a disease increase of amount of delta and aminolevulinic acid and porphobilinogen does not reach such high level as at the acute alternating porphyria. In urine and Calais the amount of coproporphyrin is considerably increased.
The Variyegatny porphyria is inherited autosomal is prepotent. The pathogeny is probably connected with disturbance of activity of enzyme of a protoporfirinogen — oxidases and increase of synthesis of delta and aminolevulinic acid. The illness is characterized by signs inherent in the acute alternating porphyria. Sometimes the renal failure develops. Abdominal pains and neurologic symptomatology arise also when using certain medicines — barbiturates, streptocides, analginum.
Urokoproporfiriya (late skin porphyria) often occurred in Russia among the persons who are abusing alcoholic beverages, had hepatitis, having contact with gasoline and hepatotoxic poisons. The majority of them has disturbances of functions of a liver. In urine the maintenance of an uroporfirin is increased generally, and the content of coproporphyrin is increased slightly, activity enzyme uroporfinogen carboxymanholes is found. These data allow to think that it is about the acquired urokoproporfiriya form. At the same time at most of relatives of patients with an urokoproporfiriya increase of maintenance of an uroporfirin in urine and coproporphyrin in Calais comes to light, in several families is available on 2 — 3 patients with an urokoproporfiriya. Noted facts do not give the grounds to completely exclude possible inheritance of an urokoproporfiriya, apparently, on autosomal dominantly type.
Urokoproporfiriya is characterized by skin symptomatology (hypersensitivity to solar radiation, a mechanical injury, a widespread thickening or thinning of skin, formation of bubbles mainly on a dorsum of brushes and the person with the subsequent development of hems, etc.). Morphological changes of skin are expressed as primary defeat of a derma, changes in epidermis are secondary. An important clinical symptom is increase in a liver, is frequent with disturbance of its functional state.
At an urokoproporfiriya in urine the maintenance of an uroporfirin, to a lesser extent — coproporphyrin is considerably increased.
Verification of the diagnosis Diagnosis of various forms hereditary erythropoietic and hepatic porphyrias is based on characteristic datas of laboratory and changes of skin. Differential and diagnostic value polyneurites, mental disorders have" abdominal pains, increase of arterial pressure, a phytodermatosis, formation of hems, hemolitic anemia, increase of level of an uroporfirin and coproporphyrin in urine and in erythrocytes, coproporphyrin and protoporphyrin to Calais, activity of enzymes.
The acute alternating porphyria should be differentiated from the plumbism which is followed by abdominal pains, a polyneuritis at which unlike an acute porphyria hypochromia anemia with basphilic stippling of erythrocytes, the high level of iron of blood serum is observed; high-quality test on porphobilinogen is more often negative.
Treatment of porphyrias
The modern clinic has no methods of pathogenetic treatment of a porphyria. Some effect at an erythropoietic uroporfiriya is observed from the splenectomy which is followed by lengthening of life expectancy of erythrocytes and release there is less uroporfirin in unit of time of the destroyed erythrocytes that leads to decrease in a photosensitization. The main way of decrease in clinical manifestations of a photosensitization of patients at separate forms of a porphyria — protection against solar radiation.
At the acute alternating porphyria the analginum and tranquilizers causing an exacerbation of an illness are contraindicated. In the presence of a pain syndrome drugs, aminazine are applied; at increase of arterial pressure — inderal or Obsidanum; for reduction of production of porphyrines intravenously enter strong solutions of glucose (to 200 g/days). Treatment adenosine monophosphate (intramusculary on 50 — 60 mg), is carried out by inosine (on 200 mg inside, 3 — 4 times a day).
Treatment of an aggravation of a hereditary koproporfiriya essentially does not differ from therapy of the acute alternating porphyria. Treatment of an urokoproporfiriya is inefficient when the patient continues to take alcoholic beverages. An effective remedy is the delagil forming a complex with porphyrines of skin and removing them with urine. Drug is appointed in small doses on 0,125 g by 2 times a week during 2 weeks, then on 0,125 g every other day during 2 weeks, at good tolerance on 0,125 g daily within 3 months. By the end of a course of such therapy at most of patients clinical displays of an illness are completely stopped, it is normalized or considerably pro-porphyrine level in urine decreases. Faster medical effect is observed at delagil combination to inosine (inosine) on 0,2 g 3 — 4 times a day within 2 — 3 months. In cases when at porphyrias medicines are inefficient, justified 3 — 4, sometimes there are more plasma exchanges with an interval of 8 — 10 days. At the same time delete 1 — 1,5 or 2 l of plasma with substitution by the adequate volume of freshly frozen donor plasma, albumine, Polyglucinum.