A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria.

Acute intermittent porphyria is a genetic disease in which endogenous hormones affect clinical expression. Premenstrual exacerbations can occur, sometimes often, in women with this disease. Gonadotropin releasing hormone analogues can prevent ovulation by reducing secretion of luteinizing hormone and follicle-stimulating hormone. In six patients with well-documented acute intermittent porphyria and frequent cyclical exacerbations, daily administration of an agonistic gonadotropin releasing hormone analogue, ([ImBzl]-D-His6,Pro9-NET)gonadotropin releasing hormone, intranasally or subcutaneously for as long as 26 months reduced or eliminated premenstrual attacks and caused only minor side effects. Adjustments in dosage or route of administration were sometimes needed. We conclude that endocrine manipulation by treatment with a gonadotropin releasing hormone agonist will prevent neurovisceral attacks of acute intermittent porphyria due to cyclical changes in endogenous hormones and is a safe alternative to exogenous steroids, which may induce attacks of this disease.

Photoprotection in erythropoietic protoporphyria: mechanism of photoprotection by beta carotene.

Erythropoietic protoporphyria is a genetic disease caused by the accumulation of protoporphyrin IX. This molecule absorbs 400-nm light and its presence is at times associated with severe cutaneous photosensitivity. The only effective treatment for this disease is oral administration of beta carotene. Several possible mechanisms of photoprotection by beta carotene were investigated using the photohemolysis of red blood cells as an in vitro model. Additional studies were done in an in vivo model which involves lethal hematoporphyrin photosensitization of white mice. The photoprotective effects of beta carotene were compared with those of alpha tocopherol, an agent which possesses some but not all the properties that have been implicated in explaining the known effectiveness of beta carotene. In the photohemolysis model, both compounds demonstrated partial protection. In hematoporphyrin-photosensitized mice, tocopherol showed some protection at high doses, while beta carotene showed greater protection at lower concentrations. Although these results suggest that photoprotective was due to free radical scavenging or singlet oxygen quenching, properties common to both agents, they do not rule out the possible role of 400-nm light absorption, a property of beta carotene alone.

Effect of desferrioxamine on the development of hexachlorobenzene-induced porphyria.

The present work deals with the effect of desferrioxamine (DF) on hexachlorobenzene (HCB)-induced porphyria in female rats with the purpose of further investigation of the role of iron in the development of this porphyria. The results obtained show that the repeated injection of DF (three times a week: 100 mg/kg each i.m.) delayed and diminished remarkably the urinary excretion of precursors and porphyrins as well as the accumulation of the latter in liver promoted by HCB (1 g/kg daily given by stomach tube). This was probably due to attenuation by DF of the alterations produced by the fungicide in the two key enzymes: porphyrinogen carboxy-lyase (PCL) and delta-aminolaevulinate synthase (ALA-S). In fact, DF by reducing liver iron levels produced a smaller decrease of the target enzyme (PCL) and a concomitant smaller induction of ALA-S. DF alone did not modify any of these variables or the liver to body weight ratio. DF added at 10(-2) and 10(-3) M to the incubation media of ALA-S and PCL did not alter either of the enzymatic activities, whether in normal or HCB-porphyric preparations. The results obtained show that DF improved the biochemical picture during HCB porphyria. They suggest that iron plays an indirect role in the decrease of PCL enzyme, possibly at the HCB metabolization step. A common iron-involving mechanism for the production of porphyria by different chlorinated compounds is suggested.

Cimetidine suppresses chemically induced experimental hepatic porphyria.

The ability of cimetidine to reduce the activity of hepatic aminolevulinic acid synthase (ALA-S) was examined in allylisopropyl acetamide (AIA) treated porphyric adult rats. A dose of 20 mg cimetidine/100 gm body weight resulted in a 50% decrease in the AIA-induced hepatic ALA-S activity compared to rats treated with AIA alone. Heme oxygenase activity was decreased 25% compared to rats treated with AIA alone. The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans.

Regulation of cadmium induced porphyria by ascorbic acid in chick embryos.

Sublethal doses of cadmium chloride (2.5, 5.0 and 10.0 mu mole/kg egg weight) were found to significantly alter the first two rate limiting enzymes of heme biosynthesis in chick embryos. Delta-aminolevulinic acid synthase activity was elevated by 2.05 and 2.11 fold with 5.0 and 10.0 mu moles of cadmium treatment respectively. However, this was reduced to 1.25 and 1.3 fold by the simultaneous administration of ascorbic acid. Blood delta-aminolevulinic acid dehydratase (ALA-D) activity was decreased by 48.4 and 55.0 per cent with 5.0 and 10.0 mu moles cadmium treatment respectively; in the presence of ascorbic acid only 18 and 24 per cent inhibition of ALA-D activity was observed. Further 1.39 and 2.08 fold accumulation of delta-aminolevulinic acid and 4.17 and 4.62 fold increase of blood porphyrins was observed in chick embryos treated with 5.0 and 10.0 mu moles cadmium respectively. This elevation of intermediate compounds of heme biosynthesis was effectively checked by the administration of ascorbic acid. Depletion of hepatic heme and free sulfhydryl level by cadmium were countered by the treatment of ascorbic acid. Hence, the present findings suggest the protective role of ascorbic acid against cadmium induced chemical porphyria in chick embryos.

Photodermatoses in the elderly.

Several photodermatoses specifically affect the elderly, and many others continue into old age. Photodermatoses present unique challenges in diagnosis and management when considered in the context of the multiple pathologies and problems of polypharmacy in this age group. This article examines the idiopathic photodermatoses, which include chronic actinic dermatitis, specifically a disease of the middle-aged and elderly. Endogenous (metabolic) and exogenous (drug and chemical) photodermatoses, as well as photo-exacerbated dermatoses, also are discussed.

Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue.

A 20-year-old Japanese female needed frequent hospitalization due to premenstrual exacerbation of hereditary coproporphyria (HCP). Intranasal buserelin acetate, a gonadotropin-releasing hormone analogue, was given to suppress her menstrual cycles. Her porphyric symptoms subsided dramatically as she became amenorrhoeic. Urinary excretion of porphyrin derivatives fell significantly. She has been free from recurrent attacks, but suffers a minor porphyric attack once in 5 years. However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use.

[Acute intermittent porphyria. A case report and family study]. / Akut intermittierende Porphyrie. Kasuistik und Familienuntersuchung

The course of acute intermittent porphyria is described in a patient who died during an acute exacerbation of the disease. An analysis of the urinary porphyrin precursors (delta-aminolaevulinic acid and porphobilinogen), the determination of toal porphyrin excretion and the separation of haem precursors in the urine according to the number of carboxylic groups demonstrate different degrees of biochemical severity in the individual consanuinious members of this patient's family. The detection of latent carriers is of particular importance since the avoidance of porphyrogenic substances is the most important prophylactic measure to be undertaken in all latent clinical cases. According to our experience, however, prophylactic measures must also be extended to young consanguineous family members with negative excretion patterns in view of the difference in age at which the disease manifests itself.

The management of porphyria in dental practice.

From time to time a patient may attend your practice with a systemic condition that you may or may not remember from the small print of your undergraduate text books. This paper describes one such systemic condition, porphyria, and its dental management. This paper also describes the use of relative analgesia as an aid to anxiety management in porphyria.

[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.

[Screening program with urinary porphyrins--application to clinical finding in latent porphyrias].

Judging from the incidence of porphyria in Japan, most cases can be diagnosed by measurement of the amount of porphyrin in the urine. Normally, the analysis of porphyrin in urine is performed by high-performance liquid chromatography but this requires about 40 minutes per specimen. However, if one simply measures coproporphyrin I and III only, then one specimen can be measured in about 10 minutes. If screening is performed using this method, those subjects in which high levels of coproporphyrin I and III are detected can undergo further test of urine, blood and feces to detect porphyrin and related materials. Using this screening methods in high school students, 2 cases of congenital porphyria were detected. One case was hereditary coproporphyria and the other was acute intermittent porphyria. If this method is added to screening methods normally used for health checkups, cases of porphyria should be detected with ease.

The cutaneous porphyrias.

The porphyrias are a group of mainly inherited disorders of heme biosynthesis where accumulation of porphyrins and/or porphyrin precursors gives rise to 2 types of clinical presentation: cutaneous photosensitivity and/or acute neurovisceral attacks. The cutaneous porphyrias present with either bullous skin fragility or nonbullous acute photosensitivity. This review discusses the epidemiology, pathogenesis, clinical presentation, laboratory diagnosis, complications, and current approach to porphyria management. Although focusing mainly on their dermatological aspects, the article also covers the management of acute porphyria, which by virtue of its association with variegate porphyria and hereditary coproporphyria, may become the responsibility of the clinical dermatologist.