[Significance of metal ion metabolism and oxidative stress in male patients with porphyria cutanea tarda]. / A fémion-metabolizmus és az oxidatív stressz jelentôsége porphyria cutanea tarda betegségben szenvedô férfiakban.

In the last decades, the role of oxidative stress and trace elements was proven to play an important role in the pathogenesis of more and more diseases. This is why a great importance is attributed lately to the antioxidant therapy, and lots of studies are dealing with this issue. In porphyria cutanea tarda (PCT) the biosynthesis of hem is damaged, because of the reduced activity of uroporphyrinogen-decarboxylase enzyme. The hem precursors are accumulating in blood, liver and skin. The hem precursors and porphyrin are eliminated with urine and stool. The enzyme defect is autosomal dominant. The skin symptoms are intensified by sun exposure. This is because the accumulation of uroporphyrins and heptacarboxylporphyrin in the skin causes photosensitivity, and the accumulated iron has a lipid-peroxidation effect. Besides the genetical origin, the alcohol consumption, the hepatotoxic drugs, estrogen and viral infections can also determine the development of the disease. The applied treatment is phlebotomy. In the case of PCT that appears in the field of liver damage, the accumulation of iron is responsible for the development of oxidative stress. The patient's redox homeostasis is changed, and the level of antioxidants is decreased. The redox state of liver and the effects of additional antioxidant treatment in phlebotomized PCT patients were determined by biochemical and trace element analytical methods. According to the clinical data, phlebotomy proved to be an effective treatment in PCT patients. Phlebotomy improved the phototoxic skin symptoms, but it did not improve the ratios of trace elements to each other in the blood of the patients.

Hemorheological status and redox homeostasis of phlebotomised porphyria cutanea tarda patients with diabetes mellitus and in moderate alcohol consumer.

Increase in porphyrin concentration is caused by the decreased activity of uroporphyrinogen decarboxylase in porphyria cutanea tarda (PCT). Iron overload, alcohol consumption and diabetes mellitus play role in the development of PCT. We investigated the hemorheological and redox-parameters from the blood of 34 male PCT patients and 10 male volunteers. The disfunctions were investigated by pathological amounts of iron and lipid metabolism. Routine laboratory and hemorheological parameters, plasma free SH-group concentration, H-donating ability and reducing power were measured by spectrophotometry. Free radical activity was determined by chemiluminometry method. The hemorheological parameters were significantly increased in all three groups of PCT patients compared to the controls. Negative correlations were observed between blood viscosity and antioxidant defence of PCT patients and in PCT patients with alcohol consumption. Plasma and erythrocyte chemiluminescent intensity was higher in PCT patients than in controls, which indicated the decrease of antioxidant defence. Hemorheological parameters were highest in patients with diabetes and in alcohol consumers. Iron overload increased free radical reactions in PCT patients, leading to pathological viscosity. Increased free radical reactions and high blood viscosity increase the risk of cardiovascular diseases.

[Treatment of acute porphyrias. The importance of follow-up of patients and carriers]. / Akut porphyriák kezelése. A betegek és hordozók gondozásának jelentósége.

Acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types of them: acute intermittent porphyria, porphyria variegata, coproporphyria and delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of their frequency. Basically the clinical picture is the same in the four types of acute porphyria. The most frequent complaints and symptoms are: cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the advanced phase, there is a red-colored urine, hyponatremia, subileus, acute psychosis and Landry-type paralysis. Without proper treatment death is caused by respiratory paralysis or serious arrhythmia. In case of suspicion of acute porphyria it is mandatory to identify the type of the acute porphyria and the actual status of the patient. The later indicates what kind of treatment should be used. In the acute phase the early therapy with heme arginate is the treatment of choice. Since the clinical symptoms are precipitated by endogenous or exogenous inducing factors--most often by drugs-, the drugs negatively affecting the heme biosynthesis should be omitted at once even in the suspicion of acute porphyria. The role of the inducing factors in the manifestation of the clinical symptoms makes possible the prevention. It is possible to avoid the inducing factors and this way to prevent the acute attack if the acute porphyrias are recognized in time and the patients and the carriers are under regular control. The patients receive special identification card and the up-to-date list of safe drugs. They can use only these drugs in any kind of illness. Other drugs should be considered as porphyrinogenic since it is impossible to predict based on their chemical structure if they negatively affect the heme biosynthesis.

[Acute porphyrias in differential diagnosis]. / Akut porphyriák a differenciáldiagnosztikában.

The characteristic symptoms for acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Usually there is an exogenous or endogenous factor inhibiting the heme biosynthesis or increasing the consumption of heme produced in already decreased amount. The most important precipitating factors are the therapeutic drugs. Therefore, certain therapeutic drugs ordered for carriers or patients with acute porphyria are serious risk factors. It is very important to identify patients and carriers with acute porphyria as early as possible and to make a close follow-up so the development of the symptoms of the life threatening acute attack could be prevented. It is very difficult to suspect the diagnosis of acute porphyria. There is a very characteristic discrepancy between the serious complaints and the actual clinical findings. The severe cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs and sensory loss are the main signs at the beginning. The specific symptoms which help to establish the diagnosis--red-colored urine, hyponatremia, tachycardia, hypertension, subileus, acute psychosis, gradually developing paresis of the lower and then the upper limbs--are characteristic for the later phase of the acute attack. Very often there is a rapid progression with Landry-type paralysis developing in days or even in hours, following respiratory paralysis or serious arrhythmia is the cause of the death. In case of suspicion of acute porphyria the patient should be directed to a department where the specific laboratory methods--measurement of the porphyrin precursors, porphyrins and their isomers in urine and feces, quantitation of protoporphyrin in red blood cells, measurement of the plasma porphyrin and enzyme activity--to diagnose the different types of the disease and the immediate specific treatment with heme arginate are possible if needed. All of these are available in the National Porphyria Center.