[Pregnancy and labor problems in patients with acute porphyria].

AIM: To evaluate the impact of developing pregnancy on porphyrin metabolism in reproductive-aged women with acute porphyria (AP). SUBJECTS AND METHODS: The prospective clinical data of 33 pregnancies were analyzed in 28 patients with the established diagnosis of AP. The latter was verified by the quantitative analysis of 24-hour urinary porphyrin excretion and the diminished activity of the pathognomonic enzyme. RESULTS: Each case was analyzed in detail according to different criteria. Poor prognostic factors for pregnancy are identified in AP. The used curation policy for pregnant patients is described. The pregnant women with occurring AP episodes are subdivided into clinical groups requiring different curation approaches. The scheme for the used working protocol is given. CONCLUSION: The accumulated experience with curating the patients with AP will be able to avoid the existing prohibitory practice, providing a way to develop a new quality of life in the patients' families.

[Molecular genetic study of acute intermittent porphyria in Russia: mutation analysis and functional polymorphism search in porphobilinogen deaminase gene].

Acute intermittent porphyria (AIP) is an autosomal dominant hereditary disease, caused by partial deficiency of porphobilinogen deaminase (PBGD), one of the key enzymes ofheme biosynthesis. This study describes molecular genetics of AIP in Russia. Mutation analysis of PBGD gene in 70 unrelated patients revealed 47 various genetic defects, 28 of which had not been described previously. Mutations 53delT and Argl 73 Trp (recorded 8 times, in total 23%) proved to be the most common in Russia. Microdeletion 53delThas monophyletic origin and was found only in Russia. Molecular genetic examination of 132 relatives of AIP patients from 40 families revealed 52 latent carriers of the disease. Low (about 10%) AIP penetrance indicates that a mutation in the PBGD gene is an important but not sufficient prerequisite for clinical manifestation of the disease. Modulation of penetrance in erythropoietic protoporphyria by coinheritance of a mutant allele and a functionally defective wild type allele of ferrochetalase gene has been shown previously. We hypothesized that similar mechanism works in AIP. Sequencing of the full length PBGD genes from unrelated AIP patients as well as SN P analysis, and the analysis of abnormal PBGD mRNA splicing showed that in case ofAIP, this hypothesis is not true and some other factors are responsible for the penetrance of this disease.

[Acute porphyrias: problem of primary diagnosis in Russia and CIS countries].

AIM: To analyse manifestations and experience in primary screening diagnosis of acute porphyrias which are rarely encountered and little known by general practitioners. MATERIAL AND METHODS: The data on 100 patients with the diagnosis acute porphyria have been analysed. Porphyrin metabolism in differential diagnosis was estimated according to standard techniques. RESULTS: Analysis of primary diagnosis of acute porphyria hepatica in Russia (region-related prevalence, duration of diagnosis, complications because of late pathogenetic treatment) demonstrates the importance of screening diagnosis of acute porphyria at the level of municipal clinics. CONCLUSION: Early diagnosis prevents severe complications of acute porphyria and reduces cost of examinations in search of accurate diagnosis.

[A case of the long course of acute intermittent porphyria].

A case of acute intermittent porphyria is described in a 37-year-old female patient treated with normasang, a drug that regulates porphyrin metabolism at the last stages of the disease. Chronic renal failure with the hypertensive syndrome, severe neurological symptoms, and vascular sclerotic changes in all organs were the symptoms of the underlying disease. Infectious complications were the cause of sepsis and favoured deteriorated multiple organ dysfunction that determined lethal exitus.

[Clinical manifestations of porphyrin metabolism disorders]. / Klinicheskie proiavleniia narushenii porfirinovogo obmena.

AIM: To characterize patients with various nosological unities [symbol: see text] of porphyria in accordance with their age, clinical symptoms, provoking factors, therapy and outcome. MATERIAL AND METHODS: Patients with acute intermittent porphyria (43), hereditary coproporphyria (8), variegate porphyria (3), porphyria cutanea tarda (7), hepatoerythropoietic porphyria (1), and hereditary erythropoietic porphyria (2) were studied. One patient was suspected of porphyria caused by deficiency of delta-aminolevulenic acid dehydrogenase. RESULTS: The patients were from the CIS. The overwhelming majority of them were young and middle-aged subjects. Rapid development of the disease and severe neurological symptoms were predominantly observed in patients with acute forms of porphyria. CONCLUSION: Early diagnosis of porphyrin metabolism disorders makes it possible to decrease abruptly the number of cases leading to severe complications, disability, and fatal outcome. The use of inexpensive methods of screening of porphyrin metabolism disorders provides a promising approach to solving this problem. These methods should be used in municipal hospitals. In addition, asymptomatic carriers of defective gene should be revealed at the preclinical stage using various methods of molecular genetic assay.

[Atypical electrolytic disorders in patients with diseases of the blood system]. / Netipicheskie élektrolitnye narusheniia u bol'nykh s zabolevaniiami sistemy krovi.

AIM: To describe and analyze rare iatrogenic disturbances of water-electrolyte and acid-base balances in systemic blood diseases. MATERIAL AND METHODS: Five cases of life-threatening electrolytic imbalance resultant from therapy in patients with hemoblastoses and a patient with acute intermittent porphyria (AIP). RESULTS: Hyperkalemia arose in 2 patients treated with cyclosporin A and trimethoprim-sulfamethoxasole. One patient developed severe arrhythmia because of hypomagnesemia following long-term therapy with aminoglycosides and amphotericin B. In one AIP patient hyponatremia ending in coma was attributed to the disease activity and infusion therapy. This was the cause of coma. In a patient with acute leukemia and pneumonia amphotericin B therapy entailed distal renal tubular acidosis and marked dyspnea which was primarily mistaken for acute respiratory failure. Pathogenetic, diagnostic and therapeutic aspects of the above water-electrolyte defects are provided. CONCLUSION: The appearance of water-electrolyte imbalance in hemoblastosis patients calls up a detailed analysis of the going-on therapy whether the imbalance is iatrogenic.