An analysis of 112 acute porphyric attacks in Cape Town, South Africa: Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity

Four forms of porphyria may present clinically with the acute attack, an episodic, severe, and potentially life-threatening manifestation characterized by abdominal and neurologic symptoms. We describe our experience with 112 consecutive attacks observed and treated in 25 patients with the 2 most common forms of acute porphyria in Cape Town, South Africa; 25 attacks in 10 patients with variegate porphyria and 87 attacks in 14 patients with acute intermittent porphyria. The remaining patient experienced more than 100 sequential, severe, and poorly remitting attacks, which are not included in our analysis. In our population, the relative risk of an acute attack in acute intermittent porphyria compared with that in variegate porphyria was 14.3 (confidence intervals, 6.3-32.7). Patients with variegate porphyria were significantly older (median age at first attack, 30 yr) than those with acute intermittent porphyria (median age at first attack, 23.5 yr; p < 0.0001), and demonstrated an equal sex ratio, whereas the male:female ratio in acute intermittent porphyria was 2:12 (p < 0.0001). There was a significant difference in the incidence of factors precipitating the acute attack. Drug exposure was a frequent precipitant of the acute attack in variegate porphyria, whereas hormonal factors were more important in acute intermittent porphyria (p < 0.00001). Patients with acute intermittent porphyria also showed a trend to earlier and more frequent recurrent acute attacks following the initial admission. Mean urine precursor levels, blood pressure, pulse rate, and heme arginate requirement were all significantly higher in patients with acute intermittent porphyria. No significant difference in the frequency of serious complications or in outcome could be shown. We describe our experience with treatment with heme arginate, and provide evidence that heme arginate results in a prompt and statistically significant improvement in symptoms. The incidence of serious complications and mortality in this series was low, confirming a trend to an increasingly good prognosis for patients with acute porphyria who receive expert treatment.     

Clinical and biochemical characteristics and genotype-phenotype correlation in 143 Finnish and Russian patients with acute intermittent porphyria

Acute intermittent porphyria (AIP), resulting from a deficiency of porphobilinogen deaminase (PBGD) in heme biosynthesis, is genetically heterogeneous and manifests with variable penetrance. The clinical outcome, prognosis, and correlation between PBGD genotype and phenotype were investigated in 143 Finnish and Russian AIP patients with 10 mutations (33G-->T, 97delA, InsAlu333, R149X, R167W, R173W, R173Q, R225G, R225X, 1073delA). Thirty-eight percent of the patients had experienced 1 or more acute attacks during their lives. The proportion of symptomatic patients has decreased dramatically from 49% to 17% among patients diagnosed before and after 1980, respectively. Patients with the R167W and R225G mutations showed lower penetrance (19% and 11%, respectively) and recurrence rate (33% and 0%, respectively) than patients with other mutations (range, 36%-67% and 0%-66%, respectively). Moreover, urinary excretions of porphyrins and their precursors were significantly lower in these patients (porphobilinogen [PBG], 47 +/- 10 vs. 163 +/- 21 micromol/L, p < 0.001; uroporphyrin, 130 +/- 40 vs. 942 +/- 183 nmol/d, p < 0.001). Erythrocyte PBGD activity did not correlate with PBG excretion in remission or with the clinical severity of the disease. Mutations R167W and R225G resulted in milder biochemical abnormalities and clinical symptoms indicating a milder form of AIP in these patients. In all AIP patients, normal PBG excretion predicted freedom from acute attacks. The risk of symptoms was highest for female patients with markedly increased PBG excretion (>100 micromol/L). Proper counseling contributed to the prevention of subsequent attacks in 60% of previously symptomatic and in 95% of previously symptom-free patients.     

正铁血红素治疗急性间歇性血卟啉症

目的 探讨正铁血红素对急性间歇性血卟啉症的治疗作用。方法 ２例ＡＩＰ均具有典型症状，尿Ｗａｔｓｏｎ－Ｓｃｈｗａｗｒｔｚ试验阳性，葡萄糖疗法对其明显效果，给予正铁血纱剂Ｐａｎｈｅｍａｔｉｎ治疗，２００ｍｇ／天，静脉输注，连用５天。结果 腹绞痛在用药２－３天后均迅速缓解。例１抽搐症状明显减轻，例１在６个月后症状复发，再次用药仍有效，随访２年昨发；例２接受随访１年，未见复发。     

Hepatic porphyria: A narrative review

Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Of these, AIP and ADP are classified as acute porphyria, PCT as cutaneous, while VP and HCP present with both acute and cutaneous clinical manifestations. Porphobilinogen levels in a spot urine sample is the initial screening test for the diagnosis of acute hepatic porphyria, and plasma with spot urine porphyrin levels is the initial screening test to approach patients suspected of cutaneous porphyria. Specific biochemical porphyrin profile for each porphyria helps in determining the specific diagnosis. Pain relief and elimination of triggering agents are the initial steps in managing a patient presenting with an acute attack. Intravenous glucose administration terminates the mild episode of acute porphyria, with intravenous hemin needed for management of moderate to severe episodes. Liver transplantation is curative and may be needed for patients with a life-threatening acute porphyria attack or for patients with recurrent acute attacks refractory to prophylactic treatment. Of the cutaneous porphyrias, PCT is the most common and is frequently associated with a combination of multiple susceptibility factors such as alcohol use, smoking, hepatitis C virus infection, HIV infection, estrogen use, and mutations of the hemochromatosis gene. Regular phlebotomy schedule and low-dose hydroxychloroquine are effective and safe treatment options for management of PCT.     

Acute intermittent porphyria in women: clinical expression,use and experience of exogenous sex hormones. A population-based study in northern Sweden

OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.     

Variegate porphyria

In temperate and cold climates the most usual presenting symptom of variegate porphyria is an acute porphyric attack, indistinguishable from that seen in acute intermittent porphyria. Increased fragility of the skin in sun-exposed areas occurs in only half of such patients, and even then is usually mild and easily overlooked. The diagnosis depends on fecal excretion of porphyrins, which is greatly increased in variegate porphyria and consists predominantly of protoporphyrin. Urinary excretion of porphobilinogen and delta-aminolevulinic acid increases only during acute attacks. There are reasons for thinking that variegate porphyria is commoner than hitherto supposed. During an acute attack a patient without skin symptoms may well be misdiagnosed as having acute intermittent porphyria, because of identical symptoms and excretion of porphobilinogen in the urine. Thus, for a correct diagnosis, every patient presenting with symptoms of acute porphyria requires a fecal analysis.     

Hematin therapy for acute porphyria.

1. A therapeutic trial of intravenous hematin is presented. Eleven cases of AIP and one of VP who did not improve with conventional treatment (high carbohydrate intake) received this new agent. 2. Urinary ALA, PBG and, when possible, uroporphyrin and coproporphyrin were used to monitor the chemical response to the treatment. Objective clinical parameters of hypertension and tachycardia were followed when present in addition to subjective estimates of acute porphyric symptomatology (abdominal pain, backache, extremity pain and paresthesias, weakness, depression, etc.). 3. At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients. Hypertension and tachycardia improved in those instances where they were observed in association with the attack. Also, subjective improvements in the clinical status of the patients were observed frequently. 4. Hematin appears to be a promising therapeutic agent for the treatment of acute attack forms of porphyria.     

The incidence of inherited porphyrias in Europe

Retrospective estimates of the prevalence of porphyrias have been reported but there has been no large scale prospective study of their incidence. The European Porphyria Network collected information prospectively over a 3 year period about the number of newly diagnosed symptomatic patients with an inherited porphyria (335 patients from 11 countries). Prevalence was calculated from the incidence and mean disease duration. The incidence of hepato-cellular carcinoma (HCC) in acute hepatic porphyria and the prevalence of patients with recurrent acute attacks of porphyria were also investigated. The incidence of symptomatic acute intermittent porphyria (AIP) was similar in all countries (0.13 per million per year; 95 % CI: 0.10 – 0.14) except Sweden (0.51; 95 % CI: 0.28–0.86). The incidence ratio for symptomatic AIP: variegate porphyria: hereditary coproporphyria was 1.00:0.62: 0.15. The prevalence of AIP (5.4 per million; 95 % CI: 4.5–6.3) was about half that previously reported. The prevalence of erythropoietic protoporphyria (EPP) was less uniform between countries and, in some countries, exceeded previous estimates. Fourteen new cases of HCC (11 from Sweden) were reported in patients with acute porphyria. Sixty seven patients (3 VP; 64 AIP: 53 females, 11 males) with recurrent attacks of acute porphyria were identified. The estimated percentage of patients with AIP that will develop recurrent acute attacks was 3–5 %. In conclusion, the prevalence of symptomatic acute porphyria may be decreasing, possibly due to improved management, whereas the prevalence of EPP may be increasing due to improved diagnosis and its greater recognition as a cause of photosensitivity.     

Medical and financial burden of acute intermittent porphyria

Introduction

A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers.

Methods

Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications, attack frequency, hospitalisation frequency, hospitalisation days related to acute porphyric attacks, frequency of heme infusions and medical healthcare costs based on hospitalisations and heme therapy.

Results

In total 11 recurrent AIP cases, 24 symptomatic AIP cases and 53 AIP carriers as controls were included. All recurrent patients reported porphyria related symptoms, such as pain, neurological and/or psychiatric disorders, and nearly all developed complications, such as hypertension and chronic kidney disease. In the recurrent cases group, the median lifelong number of hospitalisation days related to porphyric attacks was 82 days per patient (range 10–374), and they spent a median of 346 days (range 34–945) at a day-care facility for prophylactic heme therapy; total follow-up time was 243 person-years (PYRS). In the symptomatic non-recurrent group the median lifelong number of hospitalisation days related to porphyric attacks was 7 days per patient (range 1–78), total follow-up time was 528 PYRS. The calculated total medical healthcare cost for recurrent cases group was €5.8 million versus €0.3 million for the symptomatic cases group.

     

Porphyrien – was ist gesichert?

Porphyrias are caused by enzyme defects of heme biosynthesis. According to their clinical presentation and to each affected pathway, they are categorized into acute and non-acute as well as hepatic and erythropoietic porphyrias. Acute hepatic porphyrias, e.g. acute intermittent porphyria (AIP), porphyria variegata (VP), hereditary coproporphyria (HCP) and 5?aminolevulinic acid dehydratase-deficient porphyria (ALADP) are characterized by accumulation of the porphyrin precursors 5?aminolevulinic acid (ALA) and porphobilinogen (PBG) that correlate with severe abdominal, psychiatric, neurological or cardiovascular symptoms. Additionally, skin photosensitivity can occur in VP and less frequently, in HCP. Decisive for the diagnosis of acute hepatic porphyrias are a >4-fold elevated urinary excretion of ALA in ALADP and ALA and PBG in all other acute porphyrias. First-line treatment of an acute porphyria attack includes intensive care with pain management, sufficient caloric supply, strict avoidance of porphyrinogenic drugs and elimination of other triggering factors. Heme therapy is indispensable in case of developing neurological symptoms and clinical worsening despite first-line measures. Non-acute porphyrias, mainly porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP) and X?linked protoporphyria (XLP) display accumulation of porphyrins in the skin and/or liver resulting in photosensitivity up to possible liver damage. Patients with PCT benefit from iron depletion, low-dose chloroquine treatment and/or hepatitis C virus elimination. Afamelanotide is associated with better sunlight tolerance in patients with EPP and XLP. Moreover, innovative therapies that highly selectively address dysregulated steps of the heme biosynthetic pathway are currently under clinical trial.     

Effects of diabetes mellitus on patients with acute intermittent porphyria

Objectives. To study the effects of diabetes mellitus in patients with acute intermittent porphyria (AIP). Haeme deficiency in the liver of AIP patients stimulates an increase in ALA-synthase which triggers an escalating metabolic chain reaction, leading to an increase in the porphyrin content. This reaction can be reduced by treating AIP patients with haeme arginate or with glucose. Design. A population-based study of all patients >18 years of age having DNA-verified AIP (n = 328) living in the two most northerly counties of Sweden (Norrbotten and Västerbotten, with 550 000 inhabitants) of whom 16 had type 2 diabetes. Prevalence of diabetes was studied retrospectively in 26 AIP patients with hepatocellular carcinoma (HCC). Results. None of the patients showed symptoms of AIP after the onset of their diabetes. Three patients had had recurrent, severe attacks for many years but when their diabetes became manifest, their urinary ALA and PBG levels decreased and the AIP symptoms resolved, to the relief of the patients. Amongst the 26 AIP patients with HCC, only one with signs of diabetes was identified (impaired glucose tolerance test). Conclusions. This study raises the possibility that diabetes mellitus may be beneficial for patients with severe AIP.     

Acute intermittent porphyria associated with transient elevation of transaminases during an acute attack

A 44-year-old woman with acute intermittent porphyria (AIP) was admitted to Kudanzaka Hospital because of abdominal pain. A cholecystectomy was performed in another hospital without improvement. On admission, her transaminases were elevated to greater than 1,000 mU/ml. After an intravenous drip of mainly glucose, her transaminases returned to normal. Her acute attacks occurred during stress, and she died of respiratory failure after repetitive acute episodes. AIP should be included in a list of the differential diagnosis of gastrointestinal diseases, neurosis, and hysteria. This is the first case of AIP accompanied by transient marked elevation of transaminases during an acute attack.     

Premenstrual attacks of acute intermittent porphyria: hormonal and metabolic aspects - a case report.

We report the case of a 38-year-old woman with acute intermittent porphyria (AIP). Following the observation of an acute AIP attack in the patient's father, the diagnosis was established after genetic and biochemical examinations. At the age of 29, eight months after delivery of her first and only child, the patient was hospitalized due to a first proven attack of AIP. In the following years she suffered several premenstrual AIP attacks, with clinical symptoms ranging from abdominal pain to paralysis. One attack was accompanied by an increased urinary catecholamine output, strongly indicating adrenergic hyperactivity. The precipitation of acute episodes by secretion of gonadotrophins and a severe hyponatraemia due to a syndrome of inappropriate anti-diuretic hormone secretion indicated hypothalamic involvement in the pathogenesis of AIP. This patient has experienced an evolution of treatment regimens. At first, acute attacks were treated by i.v. hypertonic glucose. Afterwards propranolol was instituted as a maintenance therapy. Later on, i.v. injections of haem arginate were very successful in resolving acute AIP episodes. However, until therapy with an LHRH analogue was started, the patient continued to suffer premenstrual AIP attacks. These LHRH analogues cause hypothalamic inhibition of gonadotrophin secretion, with stabilization of endogenous ovarian steroid production at a low level, and therefore may be effective in preventing acute exacerbations of this disease. Since this patient went on a fixed regimen of an LHRH analogue combined with the lowest dose oestrogen patch her quality of life has improved substantially and she has not required hospitalization, now for over 3 years.     

Plasma porphobilinogen as a sensitive biomarker to monitor the clinical and therapeutic course of acute intermittent porphyria attacks

BackgroundAcute intermittent porphyria (AIP) is a metabolic disease affecting hepatic heme biosynthesis. The clinical course in overt disease is characterized by acute attacks of neurovisceral symptoms. Treatment is based on symptomatic relief together with carbohydrate loading and in more severe attacks heme therapy.During an acute attack the heme precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA) are produced in high amounts by the liver and are found in high concentrations in plasma and urine. These metabolites represent the acute phase reactants confirming an ongoing attack and are used to evaluate therapeutic measures.The aim of this study was to measure PBG and ALA in plasma and urine during an acute attack and to match the biochemical pattern with the clinical and therapeutical course.MethodsThree consecutive AIP patients were included during four acute attacks. Plasma PBG and ALA were measured by a LC-MS method and in urine by ion-exchange chromatography. The patients received symptomatic and glucose treatment at admission to hospital, and four days later, if necessary, heme therapy.ResultsIn the three attacks that required heme therapy, plasma PBG concentrations had further increased after admission (p = 0.01). In the patient that did not require heme therapy, plasma PBG had decreased after admission.ConclusionsBiochemical monitoring of an acute attack was more accurately reflected by plasma PBG than plasma ALA or urinary PBG and ALA. Glucose administration, in contrast to heme therapy, was not sufficient to achieve clinical and biochemical remission in the more serious attacks.     

Role of two nutritional hepatic markers (insulin‐like growth factor 1 and transthyretin) in the clinical assessment and follow‐up of acute intermittent porphyria patients

Objective. Acute intermittent porphyria (AIP) is caused by a deficiency of hydroxymethylbilane synthase. Clinical manifestations are abdominal pain and neurovisceral symptoms, accompanied by overproduction of heme‐precursors in the liver, which frequently remains long‐lasting in AIP patients. We tested the hypothesis that this condition may be associated with alterations of hepatic proteins known to be either increased or decreased in serum according to diverse pathological conditions including malnutrition, inflammation or liver disease. Design. Serum proteins were analyzed in 26 biochemically active AIP patients that were classified according to the EPI (European Porphyria Initiative) guidelines as follows: (i) patients who presented a single acute attack having remained so far free of clinical symptoms; (ii) patients who present recurrent attacks or chronic symptoms associated with exacerbations of AIP. Results. Most of the serum proteins were within normal limits, however insulin‐like growth factor 1 (IGF‐1) was decreased in 53.8% of AIP patients (z‐score = ?2.86 ± 0.37) and transthyretin (prealbumin) was found significantly decreased in 38.5% of them. The IGF‐1 z‐score was lower in group B versus group A patients (?2.66 vs. ?1.43; P = 0.024). The coincident decrease of both IGF‐1 and transthyretin was associated with worsening of the clinical condition. Conclusions. This first study in humans suggests that the clinical expression AIP is associated with a state of under‐nutrition and/or with hepatic inflammation due to the sustained accumulation of heme‐precursors. We propose the use of both IGF‐1 and transthyretin as biomarkers of disease morbidity/severity for the clinical follow‐up of AIP patients.     

Use of gonadotropin-releasing hormone analog with tibolone to prevent cyclic attacks of acute intermittent porphyria

A 25-year-old woman with a 10-year history of recurrent attacks of acute abdominal pain just before menstrual periods had acute intermittent porphyria (AIP) diagnosed when she was 23.5 years old. Many acute attacks required hospitalization. Suppression of the menstrual cycle with a gonadotropin-releasing hormone analog (GnRHa; triptorelin) and tibolone administration as add-back therapy resulted in absence of acute porphyric attacks. The patient had no acute attacks over a 1-year follow-up period. This case suggests that long-term GnRHa therapy with tibolone add-back may be a therapeutic option for patients with AIP.     

Late diagnosis of a severe attack of acute intermittent porphyria (AIP)--diagnostic dilemmas

The article presents diagnostic problems concerning the case of 54-year old woman with a delayed diagnosis of a severe attack of acute intermittent porphyria (AIP), which on admission manifested mainly as flaccid quadriplegia. The signs of neurological deficit were accompanied by changes in electrocardiographic recording that suggested acute myocardial ischaemia without apparent chest pain. Based upon a detailed history and identification of potential factors that might have triggered the attack the suspicion of acute hepatic porphyria was raised. The suspicion was confirmed by biochemical testing in the Institute of Hematology and Transfusiology in Warsaw. The treatment with glucose was administered, drugs contraindicated in porphyria were excluded, and early rehabilitation programme was instituted, which led to a marked improvement of general status and resolution of quadriplegia after 16 weeks. Parallel to the improvement of neurological status and a decrease in urinary excretion of heme precursors the normalisation of ECG changes was observed. The authors point out that differential diagnosis of abdominal pain with concomitant hyponatraemia should include an attack of acute porphyria since early administration of proper management prevents the development of life-threatening neurological signs accompanying the severe attack. The diagnosis of an attack of acute porphyria in the phase of predominant neurological signs, in the absence of abdominal pain, may be difficult and always warrants, apart from anamnestic data, the confirmation with appropriate biochemical testing.     

Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria

OBJECTIVE: To assess signs of distal neuropathy in patients with acute intermittent porphyria (AIP). DESIGN: A population-based study. SUBJECTS: All patients with DNA-verified AIP >/= 18 years of age in the four most northerly counties of Sweden. INTERVENTION: Validated neuropathic signs and tests such as monofilament test, neuropathic pain, dry feet, extensor digitorum brevis (EDB) test, loss of forefoot arch, hammer toes and ulceration. RESULTS: A total of 356 patients were registered and 339 of them (95%) participated in the neuropathy study. The chronic neurological signs were symmetrical and similar to those in type 1 diabetic patients. Significant impairment was found concerning perception, EDB test, lower leg pain, ankle and knee tendon reflexes, but not concerning dry feet, loss of forefoot arch and hammer toes, on comparing patients with manifest versus latent AIP. The neurological signs were more severe in the diabetic patients (n = 298). Five AIP patients had permanent quadriplegia after severe attacks. CONCLUSIONS: Patients with manifest AIP had significantly more signs of distal chronic, symmetrical neuropathy of axonal type than did patients with latent AIP. More grave neurological lesions appear to develop after severe attacks.     

A case of acute intermittent porphyria with acute pancreatitis.

A case of acute pancreatitis in a 29-year-old female associated with an attack of acute intermittent porphyria (AIP) is reported. Following the attack of AIP, serum pancreatic amylase originating from the pancreas increased transiently, and mild swelling of the pancreas was detected by ultrasonography. On this basis acute pancreatitis was diagnosed. Additionally, this patient had mild hepatic dysfunction. Laparoscopy disclosed diffuse slightly dark bluish pigmentation on the irregular surface of the liver. Mild fibrous dilatation of the portal area with lymphocytic infiltration was seen histologically. Acute pancreatitis and hepatic damage with AIP is extremely rare, however it is possible that these findings are etiologically connected in this patient.     

Self-rated psychosocial consequences and quality of life in the acute porphyrias

A battery of self-report psychosocial measures was mailed to 116 patients who had been referred for clinical management (clinic attenders) or laboratory diagnosis (non-clinic attenders) to the London Supraregional Assay Service Centre for Porphyria over the past decade and who tested positive for porphyria. Usable replies were received from 81 (70%) patients. Our interest focused on the prevalence of psychosocial symptoms in acute porphyrias and the perceived effects of porphyria on quality of life and patient experience. Research questions examined included (i), lifestyle factors; (ii) life events; (iii) mental health; (iv) general health; and (v) perceptions of illness of patients receiving specialist clinical management compared to respondents referred for diagnostic investigations, between patients with latent or manifest symptomology and between patients with different types of porphyria.Patients with porphyria have an impaired quality of life, particularly manifest cases, compared to controls and to diabetic patients. Depression, and particularly anxiety, is more common than in the general population or general medical outpatient attenders. Quality of life is lower in acute intermittent porphyria (AIP) than in other forms of porphyria and a significant number of patients had major life event consequences, e.g. failure to secure, or loss of, employment, limitation of family size. Patients attending a clinic providing specialist porphyria advice, management and counselling received some perceived lifestyle benefits.