Date of publication: 2014-06-16
Version: 3.0
E80.2A
Porphyria is the collective name for eight hereditary diseases, all caused by deficiencies of certain enzymes (proteins which regulate the speed of different chemical reactions) necessary for the production of heme, the red pigment in the blood. The name is derived from porphyros, the Greek word for purple. Acute intermittent porphyria (AIP) is the most common form of porphyria in Sweden. It can give abdominal pain, often in combination with neurological and psychiatric symptoms. In later stages, the liver and kidneys may be affected. The information in this material is confined to acute intermittent porphyria. The Swedish Board of Health and Welfare’s database of rare diseases also contains information on erythropoietic protoporphyria (EPP).
Acute intermittent porphyria was first described in medical literature in the late 19th century. In the beginning of the 20th century Einar Wallquist, a general practitioner working in Arjeplog, became aware of the disease and was the first to report cases in Sweden. Locally it was named the “family disease,” the “red disease,” or “Arjeplog disease.”
In 1937, Swedish physician Jan Waldenström published an academic thesis based on a study of 106 people with acute intermittent porphyria. The study gained an international reputation and the disorder came to be known as “Swedish porphyria.” However, as the condition typically manifests in acute episodes at varying intervals, Waldenström named it acute intermittent porphyria.
Acute intermittent porphyria occurs worldwide, but in Sweden it was initially regarded as a disease of the north as the highest prevalence rates are found in the provinces of Norrbotten and Västerbotten. In some areas the prevalence of carriers of the disease can be as high as one in 200, or even one in 50. In Sweden as a whole, prevalence is estimated at 10 per 100,000 inhabitants. In the whole country there are approximately 1,000 carriers of the mutated gene, of which roughly 50 per cent live in the four northernmost Swedish counties. For this reason, the disease is no longer regarded as a disease limited to the north of the country.
Acute intermittent porphyria is caused by a mutation in the PBGD gene, located on chromosome 11 (11q23.3). This gene regulates the production of the enzyme porphobilinogen deaminase (PBGD). The enzyme is necessary for the cells’ production of heme, the red element in blood. One of heme’s important functions is to enable the liver to break down medication. The mutation causes a porphobilinogen deaminase deficiency.
In the cells of the body, heme is produced in a sequence of eight steps, each of which contributes to the overall process. Porphyrins are substances which the body uses to produce heme. In acute intermittent porphyria the third step of the process, regulated by enzyme PBGD, functions at only approximately 50 per cent of normal. However, this 50 per cent of residual PBGD activity is, in most circumstances, sufficient to ensure an uninterrupted flow of heme, so there are no clinical symptoms of enzyme deficiency.
In certain situations, cells need to accelerate production of heme to such an extent that the defective third step of the process cannot meet the requirements. The result is that two substances, PBG ( porphobilinogen) and ALA (aminolaevulinic acid), which PBGD usually helps to convert, start to accumulate. The urine of the patient may turn red from a surplus of PBG, while ALA is thought to damage the nervous system. The causes of long-term damage to the liver and kidneys have not yet been established.
The most common agents precipitating attacks of acute porphyria are certain prescription drugs, sex hormones, alcohol, chemical solvents, physical or mental stress, fasting and infection. They increase the need of the liver for heme and accelerate its production process, meaning that the PBGD step can no longer cope with demand.
The inheritance pattern of acute intermittent porphyria is autosomal dominant. This means that one of the parents has the enzyme deficiency, having one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the enzyme deficiency and do not pass it down. Many people who inherit the mutated gene never develop symptoms and remain free from attacks their whole lives. The risk of developing the disease can depend on where in the gene the mutation is located. Certain mutations in the PBGD gene, including the type that is most common in Sweden, may give rise to more severe forms of illness.
There are two types of symptoms associated with acute intermittent porphyria: acute symptoms presenting as sudden attacks of abdominal pain and neurological problems, and longer-term complications which after many years eventually affect the liver and kidneys.
Acute symptoms vary greatly. The entire nervous system is affected during attacks but symptoms are generally transient. The brain, the peripheral nervous system and the autonomous nervous system are affected to different degrees. Metabolic products which accumulate in the body including, it is thought, ALA (aminolaevulinic acid) can directly or indirectly affect nerve tissue. Impaired heme production can possibly lead to impaired function of certain important enzymes which are reliant on heme, particularly in the liver. Intermittent neurological symptoms such as seizures and temporary loss of vision may be caused by the contraction of blood vessels, obstructing blood flow to certain areas of the brain. Other symptoms, including rapid heart rate and high blood pressure, are usually caused by elevated levels of stress hormones.
Vomiting and kidney problems may upset the fluid-salt balance. During some attacks the hypophysis may respond by producing increased amounts of ADH, an anti-diuretic hormone which reduces the kidneys’ water output. Higher water levels dilute the blood and the concentration of sodium falls. If sodium falls below a critical level, there is a risk that brain functions will be affected and the patient may experience confusion, hallucinations, numbness, paralysis or epileptic seizures. Very low blood sodium concentrations may cause permanent brain damage. Low blood magnesium concentrations may explain the dangerous incidences of heart arrhythmia which sometimes occur in people with the disease.
Most people with a mutation in the PBGD gene experience no symptoms. However, about a third experience occasional or, more rarely, recurrent attacks. It is seldom that pre-pubescent children show symptoms of acute porphyria. Usually the first attacks occur in the 20’s or 30’s but the disease can also present in the teens, in middle age or, in exceptional cases, old age.
Abdominal pain
The most characteristic symptom is acute abdominal pain, which can be very severe and similar to other extremely painful conditions, such as ileus (blockage of the intestine), kidney stones or gall stones. The duration of the attack can range from a couple of days to one or two weeks if not treated. The pain is often diffuse and extends over the whole abdominal area, but may also affect the lower region or one side only. The abdominal wall is not rigid, as in peritonitis (inflammation of the peritoneum). The pain may be excruciating, and the usual pain medications may not provide relief. Even morphine may have only limited effect.
During attacks urine may become red coloured. This is a signal that the step in heme production which is regulated by PBGD is not functioning properly, and that PBG (porphobilinogen) is accumulating and being excreted in the urine. Red-coloured urine that does not contain blood always indicates the possibility of an attack of acute intermittent porphyria. The absence of red-coloured urine does not in itself exclude the presence of acute intermittent porphyria.
High blood pressure is common and the pulse rate may remain elevated throughout the attack. This is assumed to be caused by high levels of stress hormones. The first signs of an attack are often nausea, vomiting, severe constipation, restlessness and insomnia.
Neurological symptoms
Peripheral nerve damage can cause pain in the muscles and the back, common symptoms in acute attacks. Other neurological symptoms include numbness and muscle weakness that may rapidly progress to paralysis. If paralysis occurs, the condition may last for several months, but in most cases the patient makes a full recovery. In severe cases, respiratory tract musculature is affected, weakening the voice and causing breathing problems. Less common symptoms include decreased sensory skin response, temporary problems emptying the bladder or transient vision loss. Muscle and back pain are other symptoms.
Psychiatric symptoms
If the central nervous system is affected, transient psychiatric problems may present. Common symptoms include anxiety and irritability, depression and sleeplessness. Confusion, delusions and hallucinations may also arise.
Precipitating factors
The specific trigger of an attack of porphyria can often be identified. Precipitators of an attack include:
- stress, physical or mental
- certain medication, including several drugs used to treat psychiatric disorders
- sex hormones, including those in oral contraceptives, or hormonal changes before menstruation
- infections
- alcohol
- fasting, dieting or insufficient nutrition
- organic solvents, used for example in paint, varnish or cleaning products
Physical or mental stress and unsuitable medication are the most common precipitators of an attack. The next most common precipitator in women is normal premenstrual hormonal fluctuations. Increased production of stress and sex hormones increases the need for certain enzymes which are dependent on heme for normal functionality. Infections or insufficient nutrition in combination with fasting, dieting, or sport requiring exertion over long periods of time, can cause a heme deficiency as the breaking down process accelerates, as does the rate of heme production.
Long term complications
Long term complications include high blood pressure, kidney damage and liver cancer. People with an inherited PBGD deficiency who have not experienced any acute episodes do not have a higher risk of high blood pressure than normal. Approximately 50 per cent of all those who suffer attacks of acute intermittent porphyria develop hypertension.
People who have previously shown symptoms of enzyme deficiency are also more likely to suffer kidney damage. It is thought that the high concentrations of stress hormones during attacks damage the blood vessels of the kidneys. In those who experience repeated attacks it is not uncommon for kidney function to deteriorate, although initially kidney damage may develop slowly without giving rise to symptoms.
Primary liver cancer, which originates in the liver, is normally a rare condition in Sweden. However, it manifests more frequently people in people affected by acute intermittent porphyria who are over the age of 50. Regular (at least once a year) ultrasound examinations of the liver increase the chance of early diagnosis and treatment.
Psychological and social consequences
Like many other chronic disorders which impose restrictions on one’s way of life, acute intermittent porphyria can be difficult to live with. The extent to which the quality of life is affected by the illness itself, or by fear of acute attacks, varies between individuals. The person’s social situation also greatly affects how distressing he or she feels the disease to be. The fear of serious or long term illness can be great. The individual’s work situation may also become difficult if he or she experiences frequent attacks of the disease.
Laboratory analyses are always required to confirm a diagnosis. At the stage in the disease where symptoms present, elevated levels of metabolites (the intermediates and products of metabolism) are found in blood, urine or faeces.
Elevated concentrations of PBG in the urine are a sign that acute porphyria is manifesting. This is not found in any other medical conditions. Normal concentrations of ALA and PBG in urine rule out a bout of acute porphyria, but do not exclude the latent form of the condition.
The complex nature of porphyria’s metabolites is the reason why more advanced diagnostic methods are often required for a firm diagnosis. A DNA analysis will confirm the diagnosis. It can also be used to detect the presence of latent porphyria, and to help establish which family members are carriers of the disease.
An attack of acute porphyria can be difficult to distinguish form other acute abdominal problems, but unexplained abdominal pain combined with neurological and psychiatric symptoms should give rise to suspicions of acute intermittent porphyria. It is very important that the correct diagnosis is made. With rapid diagnosis and adequate treatment symptoms can always be controlled. If the diagnosis is missed however, the condition may become life-threatening. If an attack of acute porphyria is suspected, a urine sample should be analysed as soon as possible to establish evidence of elevated levels of PBG and ALA.
It is important to be aware that abdominal pain in people with acute intermittent porphyria may be caused by other, sometimes serious, conditions which are also characterized by abdominal pain. It is therefore essential to eliminate the presence of blood or myoglobin, (a by-product from the breaking down of muscle tissue) in the urine.
It is important to determine carrier status. People who have inherited a mutated PBGD gene should be informed of this, so they can find out what to do to avoid developing symptoms after puberty. A person who belongs to a family with acute intermittent porphyria but who has not inherited the mutated gene must also be informed that he or she does not run a risk of developing the disease and therefore does not need to take any special precautions.
All carriers of acute intermittent porphyria in the same family share the same mutation. When the disease is known in a family, PBGD deficiency can be identified at birth with the help of a DNA analysis. Prenatal diagnosis is possible. Early identification of the PBGD mutation means a child can become accustomed to avoiding factors which can precipitate an attack well before he or she reaches puberty.
The national porphyria registry, located at the laboratory at the Porphyria Centre Sweden, may help the laboratory determine the specific mutation associated with a particular family and select the appropriate method of analysis. If there is no registered family history, genetic analysis will be more time-consuming. In these cases, identification of the affected gene is made with the help of slightly less reliable measurements, including enzyme activity in the blood and the level of PBG in the urine. The investigation will also include a DNA analysis if results from tests on samples of blood, urine and, sometimes faeces, indicate this.
Preventive measures
A person with acute intermittent porphyria should be well informed about the disease. One aspect of treatment therefore involves information and instruction. It is important for the whole family to know what can cause attacks and what to do if symptoms present. Most carriers of the mutated gene can avoid or reduce the risk of attacks by consistently trying to avoid exposure to precipitating factors. They include:
- Stress. Physical and/or psychological stress are the most common causes of acute attacks. How much stress an individual can cope with varies greatly.
- Medication. Lists of drugs which should and should not be used are available from the relevant patient association and are also available on the internet. (See under “Information material “).
- Sex hormones. Oral contraceptives are a common cause of porphyria attacks in young women. Although new low-dose birth control pills are less likely to provoke an attack, they should be prescribed restrictively, preferably after consultation with both an experienced gynaecologist and a porphyria specialist.
- Infections. Common colds, flu, urinary tract infections or other infections increase the risk of an attack. If individuals are suffering from infections it is strongly recommended that they avoid other precipitating factors.
- Alcohol and smoking. All carriers of acute intermittent porphyria mutation should restrict their intake of alcohol. The same applies to smoking.
- Dieting, fasting. Not eating enough can precipitate an attack of porphyria. Meals should be regular. When experiencing symptoms, or when exposed to factors which can precipitate them, meals should be rich in carbohydrates. If weight loss is desired, a dietician with experience of working with acute intermittent porphyria should be consulted. Diets based on low consumption of carbohydrates, such as the GI diet, are not recommended. Carriers of the mutation should also be aware that sports or physical activities requiring exertion over long periods of time and with limited opportunities for food intake should be avoided.
- Solvents. Jobs involving the use of solvents are not suitable for carriers of acute intermittent porphyria. All exposure to solvents should be avoided.
Preventive hormone treatment
A few women have recurring attacks related to their menstrual cycle. With great care, oral contraceptives may be taken, as can hormones which control the production of sex hormones and regulate hormone fluctuations, as they may help prevent attacks. These treatments must be carried out under the close supervision of a gynaecologist in collaboration with a porphyria specialist.
Pregnancy
Pregnant women with the diagnosis should learn to detect characteristic signs of acute intermittent porphyria and know what to do if they experience symptoms. As soon as the pregnancy is confirmed, the concentration of PBG in the urine should be measured. The result can be used to compare with the results of future tests carried out in cases of suspected porphyria attacks. Even if vomiting during pregnancy is common in normal pregnancies, it should be recognized that it may also be caused by an attack of porphyria. The colour of the urine should be monitored as a precautionary measure and a physician contacted if it changes, as this may be a sign that the disease is becoming active.
To help protect against the stress involved in labour, additional sugar should form part of the woman’s diet in the days before delivery. Local anaesthetics and drugs used to speed up delivery should be selected from the special list of drugs approved for use in Sweden.
Surgery
Although many carriers of the mutated gene can take most drugs without an attack of porphyria being precipitated, it must be ensured that medication and anaesthetics do not increase the risk of such attacks. The lists of medication in the booklet distributed by the patient association, The Swedish Porphyria Association (see under “Organizations for the disabled/patient associations etc.”), or in a relevant database, and/or a specialist in acute intermittent porphyria, should always be consulted. Barbiturates, which are sometimes used in anaesthesia, must never be given. Sulphonamides must never be used to treat infections.
Prior to any operation a neurological and psychological assessment should be carried out to judge what complications associated with porphyria may arise after the procedure. The strain on the patient in association with the operation, in the form of increased stress, fasting and medication, can be counteracted by providing glucose.
Treatment during acute attacks
During an attack the patient’s fluid balance, blood sodium and magnesium concentrations should all be monitored. Daily controls should be continued until the attack is over as sodium and magnesium concentrations may drop quickly to life-threatening levels. If levels fall, supplements containing these particular substances should be administered intravenously to prevent complications.
A glucose solution administered immediately at the onset of an attack may halt it. Since this treatment generally has no effect on other medical conditions, it may be administered at an early stage.
The use of human hemin (heme arginate) is even more effective than glucose, and in severe attacks should always be administered at an early stage. Heme arginate is administered intravenously in a twenty per cent albumin solution given at a clinic experienced in porphyria treatment, or in collaboration with a porphyria specialist. As a rule it takes between two and six days for porphyrin precursor levels to normalize and for pain to disappear. During the attack symptoms should be treated with appropriate medication. (See under the heading “Information material. “)
Abdominal pain may be so severe that morphine or other opiates are required. Tranquillisers, sleeping pills and a calm environment may help to relieve pain. Medication may also have a beneficial effect on nausea and vomiting. Beta blockers can be used to stabilise the heart rate and lower blood pressure.
Levels of PBG in the urine can be used to indicate disease activity, even after the attack. Muscle function should be carefully monitored, as paralysis of the hands and feet may suddenly occur. Physiotherapy may be required.
Many people, if they do not have neurological symptoms and have previously experienced attacks, prefer to remain at home to deal with them themselves.
Regular monitoring
In order to prevent long-term complications it is important that individuals with symptoms caused by acute intermittent porphyria have their kidney function and blood pressure regularly monitored. From the age of around 50, an annual ultrasound examination should be carried out. In this way impaired kidney function and high blood pressure can be detected at an early stage, and liver tumours treated in time.
Regular examinations of the liver should also be carried out in middle-aged carriers of the mutated gene, even if they have not yet experienced symptoms.
Personal medical information cards
When in contact with healthcare services, it is important that the person with PBGD deficiency is not prescribed medication or treatment which is unsafe for people with acute intermittent porphyria, and which can provoke an attack or exacerbate the disorder. To ensure that inappropriate medication and treatment are not prescribed, all carriers of acute intermittent porphyria should be provided with a personal medical information card and a list of suitable and unsuitable drugs to warn medical professionals of the dangers. In Sweden, the personal medical information card is signed by the physician at Porphyria Centre Sweden who was responsible for the diagnosis.
It can be of great help to healthcare professionals if a note, if possible containing a description of the individual’s treatment regime, is added to the patient file of anyone who suffers recurrent attacks of acute intermittent porphyria. The note should specify acute interventions and provide contact information so a porphyria specialist may be contacted for further information.
The personal medical information card should be carried at all times and the person with the disease should always be able to provide medical professionals with lists of suitable medications, and medications which are unsafe for use with patients with acute intermittent porphyria.
Other points
As with many other diseases, acute intermittent porphyria can lead to feelings of isolation and loneliness. Friends and family are important, but it can be a relief to meet others with the same condition. It can also be useful to discuss the condition with a psychologist or social worker. Friends and family are important, but it can be a relief to meet and share experiences with others with the same condition. It can also be useful to discuss the condition with a psychologist or social worker.
It is important to identify the trigger of an attack of acute intermittent porphyria, whether it is a new medicine, hormone therapy or stress, so it can be avoided in the future. Mild symptoms can be self-managed. For example, sugar intake can be increased by consuming four to six sugar cubes an hour, or by drinking fruit juice. Swedish pharmacies sell ready-to-drink glucose solutions with high levels of carbohydrates (for example Nutrical). Over-consumption of sugar increases the risk of weight gain.
Other factors that may alleviate symptoms include sufficient rest, regular meals and an adequate carbohydrate intake. Paracetamol is suitable for pain relief.
The Porphyria Centre Sweden
CMMS, L7:05, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 714 45, fax: +46 8 517 714 74, email: porfyricentrum@karolinska.se, www.karolinska.se/porfyri.
The Porphyria Centre Sweden is part of CMMS, (Centre for Inherited Metabolic Diseases) and has a specialist laboratory for diagnosing and monitoring types of porphyria and works with molecular biological and biochemical methods. All gene identification in Sweden is carried out at the laboratory. The Centre provides telephone consultations and has a national, computer-based register organized by family.
Porphyria Clinic, Söder Hospital
Medical Department, Stockholm South General Hospital (Södersjukhuset), SE-118 83 Stockholm, Sweden. Tel: +46 8 616 10 00.
The Porphyria Centre Sweden
Senior Physician Eliane Sardh, Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 714 73, fax: +46 8 517 714 74, email: eliane.sardh@karolinska.se.
Senior Physician Pauline Harper, Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Solna, SE-117 76 Stockholm, Sweden. Tel: +46 8 517 714 47, fax: +46 8 517 714 74, email: pauline.harper@karolinska.se.
Ylva Floderus PhD (geneticist), Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Solna, SE-117 76 Stockholm, Sweden. Tel: +46 8 517 714 52, fax: +46 8 517 714 74, email: ylva.floderus@karolinska.se.
Specialist Physician Daphne Vassilou, Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00, email: daphne.vassilou@karolinska.se.
Porphyria Clinic, Söder Hospital
Senior Physician, Eliane Sardh, Department of Internal Medicine, Stockholm South General Hospital (Södersjukhuset), SE-118 83 Stockholm, Sweden. Tel: +46 8 61 61 000, fax: +46 8 61 63 116, email: eliane.sardh@sodersjukhuset.se.
The Norrland Region
Professor Christer Andersson, General Medicine, Institute of Public Health and Clinical Medicine, Norrland University Hospital, SE-901 85 Umeå, Sweden. Tel: +46 90 785 35 21, email: christer.andersson@fammed.umu.se.
In collaboration with Porphyria Centre Sweden, The Swedish Porphyria Association (RMP) organizes information meetings. Contact the Association for further information. (See under the heading, “Organizations for the disabled/patient associations etc.”)
The Swedish Porphyria Association (RMP), Karolinska University Hospital, Huddinge, MP 96, SE-141 86 Stockholm, Sweden. Tel: +46 8 711 56 09, email: porfyrisjukdomar@gmail.se, www.porfyri.se.
Rare Diseases Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, fax: +46 8 546 404 94. Email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a national association representing people with rare diseases and varying disabilities.
The Porphyria Centre Sweden develops care programmes for porphyria. Currently some clinics in Sweden provide consultations and information with the support of the Porphyria Centre. (See under the heading “Resource personnel.”)
Research at the Porphyria Centre Sweden focuses on improving the reliability of laboratory analyses. This is carried out in collaboration with Porphyria Centres in Europe, (European Porphyria Network, EPNET). Work is also directed at developing and testing new, alternative treatments for porphyria. Another project is to identify appropriate and inappropriate drugs for patients with acute porphyria, as well as updating the Drug Database for Acute Porphyria and the Swedish Drug Information Database (See under “Information Material.”)
Short summaries of all the database texts are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version, and then clicking on the leaflet icon which will appear under, “Mer hos oss” in the column on the right-hand side.
The Drug Database for Acute Porphyria includes lists of suitable and unsuitable medications in cases of acute porphyria. It is regularly updated by The Swedish Porphyria Association (RMP) in collaboration with Porphyria Centre Sweden. Order from: The Swedish Porphyria Association (RMP), Karolinska University Hospital, Huddinge, MP 96, SE-141 86 Stockholm, Sweden. Tel: +46 8 711 56 09, email: porfyrisjukdomar@gmail.com.
The Swedish Porphyria Association (RMP) publishes information for patients and health care professionals. The brochures below can be ordered from RMP’s office, tel: +46 8 711 56 09.
- The Swedish Porphyria Association (RMP). Kort information om porfyrisjukdomarna och om hur patientföreningen arbetar. (In Swedish only.)
- Kost vid akut porfyri. Upplysningar om lämplig mathållning om man är anlagsbärare av akut porfyri. (In Swedish only.)
Databases
The Swedish Drug Information Database includes lists of suitable and unsuitable medications for use in cases of acute porphyria. www.drugs-porphyria.org.
European Porphyria Network (EPNET), www.porphyria-europe.com.
Andersson C, Wikberg A, Stegmayr B, Lithner F. Renal symptomatology in patients with acute intermittent porphyria. A population-based study. J Intern Med 2000; 248: 319-325.
Andersson C, Innala E, Bäckström T. Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden. J Intern Med 2003; 254: 176-183.
Blom H, Andersson C, Olofsson B O, Bjerle P, Wiklund U, Lithner F. Assessment of autonomic nerve function in acute intermittent porphyria; a study based on spectral analysis of heart rate variability. J Intern Med 1996; 240: 73-79.
Bylesjo I, Wikberg A, Anderson C. Clinical aspects of acute intermittent porphyria in northern Sweden: a population-based study. Scand J Clin Lab Invest 2009; 69: 612-618.
Deybach JC, Badminton M, Puy H, Sandberg S, Frank J, Harper P et al. European porphyria initiative (EPI): A platform to develop a common approach to the management of porphyrias and to promote research in the field. Physiol Res 2006; 55: S67-S73.
Elder G, Harper P, Badminton M, Sandberg S, Deybach JC on behalf of the European Porphyria Network (EPNET) investigators. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis 2013; 36: 849-857.
Floderus Y, Shoolingin-Jordan P, Harper P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin Genet 2002; 62: 288-297.
Harper P, Sardh E.Management of acute intermittent porphyria. February 28, 2014. (doi:10.1517/21678707.2014.891456)
Harper P, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10: 444-455.
Innala E, Andersson C. Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden. J Intern Med 2011; 269: 538-45.
Sardh E, Andersson DEH, Henrichson A, Harper P. Porphyrin precursors and porphyrins in three patients with acute intermittent porphyria and end-stage renal disease under different therapy regimes. Cell Mol Biol 2009; 55: 66-71.
Sardh E, Wahlin S, Björnstedt M, Harper P, Andersson DEH. High risk of primary liver cancer in a cohort of 179 patients with acute hepatic porphyria. J Inherit Metab Dis 2013; 36: 1063-1071.
Thunell S. Porphyrins, porphyrin metabolism and porphyrias. I. Update. Scand J Clin Lab Invest 2000; 60: 509-540.
Thunell S, Harper P, Brock A, Petersen NE. Porphyrins, porphyrin metabolism and porphyrias. II. Diagnosis and monitoring in the acute porphyrias. Scand J Clin Lab Invest 2000; 60: 541-60.
Thunell S. (Far) Outside the box: Genomic approach to acute porphyria. Physiol Res 2006; 55: S43-S66.
Thunell S, Floderus Y, Henrichson A, Harper P. Porphyria in Sweden. Physiol Res 2006; 55; S109-S118.
Thunell S, Pomp E, Brun A. Guide to drug porphyrogenicity prediction and drug prescription in the acute porphyrias. Br J Clin Pharmacol 2007; 64: 668-679.
Wahlin S, Harper P, Sardh E, Andersson C, Andersson DE, Ericzon BG. Combined liver and kidney transplantation in acute intermittent porphyria. Transpl Int 2010; 23: e 18-21.
OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim
Search: acute intermittent porphyria
GeneReviews (University of Washington)
www.genetests.org (click on GeneReviews, then Titles
Search: acute intermittent porphyria
The Swedish Information Centre for Rare Diseases produced and edited this information material.
The medical experts who wrote the original text were Associate Professor Folke Lithner (†), Norrland University Hospital, Umeå, and Associate Professor Stig Thunell, The Porphyria Centre Sweden, Karolinska University Hospital, Stockholm, Sweden.
The material has been revised by Associate Professor Pauline Harper, Porphyria Centre Sweden, Karolinska University Hospital, Stockholm, Sweden.
The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.
An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.
Date of publication: 2014-06-16
Version: 3.0
Publication date of the Swedish version: 2013-12-18
For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.