Date of publication: 2010-11-11
Version: 2.2
E80.2A
Porphyria is the collective name for eight hereditary diseases. They are all caused by deficiencies of certain specific proteins (enzymes) necessary for the production of heme, the red pigment in the blood. The name is derived from porphyros, the Greek word for purple. The information provided here concerns one of the four acute porphyrias – acute intermittent porphyria (AIP). The Swedish Board of Health and Welfare’s database of rare diseases also contains information on erythropoietic protoporphyria (EPP).
Acute intermittent porphyria (AIP) is the most common of the acute porphyrias in Sweden. It causes abdominal pain, often in combination with neurological and psychiatric symptoms. In later stages, renal failure and liver cancer may occur.
Acute intermittent porphyria was first described in medical literature in the late 19th century. Dr. Einar Wallquist in Arjeplog, Sweden was the first to report cases in a family in the early years of the 20th century. Locally it was named the “red disease,” on account of the red urine characteristic of the disorder, or “Arjeplog disease,” referring to the small community where prevalence was highest.
In 1937, the Swedish physician Jan Waldenström published a 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 incidence rates are found in the provinces of Norrbotten and Västerbotten. In some areas the incidence of carriers of the disease can be as high as one in 200, or even one in 50. In Sweden as a whole it is estimated that there are approximately 10 carriers per 100,000 inhabitants i.e. a total of approximately 1000 carriers of the mutated gene. The disease is no longer regarded as a disease limited to the north of the country.
Porphobilinogen deaminase (PBGD) is one of eight enzymes necessary for the formation of heme, an essential component of vitally important proteins in the body. The gene responsible for the production of PBGD was identified in the late 1980´s. Acute intermittent porphyria is the name of the disease caused by damage to gene PBGD and impairing the activity of the PBGD enzyme, resulting in a loss of approximately 50 per cent of normal cellular activity.
The disorder underlying acute intermittent porphyria is PBGD deficiency, while the term acute intermittent porphyria refers to PBGD deficiency expressed in clinical symptoms. The individual who is deficient in PBGD, but does not show clinical symptoms, is often referred to as an AIP gene carrier. To date (June 2010) more than 300 mutations giving rise to PBGD deficiency have been recognized, 42 of them in Sweden.
In the cells of the body, heme is produced in a sequence of eight steps, the third of which is controlled by the enzyme PBGD. The approximately 50 per cent of residual PBGD activity in acute intermittent porphyria is, under most circumstances, sufficient to keep up an uninterrupted flow of heme, causing no clinical symptoms of enzyme deficiency. However, under certain metabolic circumstances a need may arise to accelerate heme production to a degree that the defective third step becomes unable to keep up with demand. Under such circumstances, two substances involved in heme production, i.e. porphobilinogen (PBG) and aminolaevulinic acid (ALA), will accumulate in the body. The urine of the patient turns red from renal excretion of surplus PBG and clinical symptoms develop, probably due in large part to the action of ALA on the nervous system. The causes of possible long-term damage to the liver and kidneys have not yet been established, but seem to be associated with the accumulation of ALA and PBG.
Several factors increase cellular demand for heme. In such cases, because of the PBGD deficiency the body may be unable to cope with the accelerated biosynthesis rate, with the result that clinical manifestations of enzyme deficiency develop. 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.
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 gene PBGD, for example the type that is most common in Sweden, may give rise to more severe forms of illness than others.
Acute symptoms affect 10 to 30 per cent of carriers once or several times during their lives and typically include sudden attacks of abdominal pain and neurological symptoms. Some of the individuals who experience acute attacks later develop severe symptoms from liver and kidneys.
Acute symptoms vary greatly. The entire nervous system is affected during attacks but symptoms are generally intermittent. The brain, the peripheral nervous system and the autonomous nervous system are affected in different degrees. The brain controls mental functions such as motor skills, and receives and interprets sensory impressions. Peripheral nerves transmit signals to muscles and sensory information to the brain. The autonomous nervous system controls involuntary physical functions. 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, in turn, causes a decrease of cellular energy and damage to nerves. 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. Contractions in the blood vessels of the intestines may explain the frequently very severe abdominal pain. 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 PBGD deficiency experience no symptoms. About a third experience occasional or, more rarely, repeated 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 is red. This is a signal that the step in heme production regulated by PBGD is not functioning properly, and that PBG (porphobilinogen), is accumulating and being excreted in the urine. Where urine is red but does not contain blood an attack of acute intermittent porphyria may be suspected.
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 numbness and muscle weakness that may rapidly progress to paralysis. 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 or back pain also occurs. If paralysis occurs, the condition may last for several months, but in most cases the patient makes a full recovery.
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 types used to treat psychiatric disorders
- sex hormones, oral contraceptives for example 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, followed by premenstrual hormonal fluctuations. Often there is a combination of precipitating factors. Increased production of stress and sex hormones increases the need for certain enzymes, which are in turn 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 accelerate the breaking down of heme and precipitate an attack of acute porphyria.
Long term complications
Long term complications include high blood pressure, kidney damage and liver cancer. Asymptomatic carriers have no higher risk of hypertonia than people with congenital PBGD deficiency. Approximately 50 per cent of all those who suffer attacks of acute intermittent porphyria develop hypertonia.
People who have previously shown symptoms of enzyme deficiency are also more likely to suffer kidney damage, as 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 originates in the liver and is normally a rare condition in Sweden. However, it manifests more frequently in older people affected by acute intermittent porphyria. Regular (at least once a year) ultrasound examinations of the liver using contrast agents increase the chance of early diagnosis and successful surgical intervention.
Social and psychological 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 and depends above all, on how the enzyme deficiency develops in each individual case. 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 is frequently ill.
An attack of acute intermittent porphyria can be difficult to distinguish from other types of acute abdominal conditions.
In someone with PBGD deficiency, 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, as 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 intermittent porphyria is suspected, a urine sample should be analysed as soon as possible to provide 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 characterised by abdominal pain. It is therefore essential to eliminate the possibilities of blood or myoglobulin, (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 gene should be informed of this, so they can find out what to do to avoid developing symptoms after the onset of 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 have the same underlying mutation. When the disease is known in a family the diagnosis of PBGD deficiency can be made at birth with the help of a DNA analysis of the blood from the umbilical cord, or later, a normal blood test. If the mutation is known, prenatal diagnosis is possible. Early identification of the porphyria gene means a child can become accustomed to avoiding factors which can precipitate an attack well before he or she reaches puberty.
With the help of a carrier register, the laboratory at the Porphyria Centre Sweden can determine the specific mutation associated with a particular family and select the appropriate method of analysis. If there is no registered family history, 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 concentrations in the blood and the level of PBG in the urine.
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 or psychological strain is one of the most common triggers of attacks. How much stress a person 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 the individual is suffering from an infection it is strongly recommended he/she avoids other precipitating factors.
- Alcohol. All carriers of acute intermittent porphyria mutation should restrict their intake of alcohol.
- Fasting, dieting. Not eating may trigger an attack. 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. Sports or physical activities requiring exertion over long periods of time and with limited opportunities for food intake should also be avoided.
- Solvents. Jobs involving the use of solvents are not suitable for AIP carriers. All exposure to solvents should be avoided.
Preventive hormone therapy
A few women have recurring attacks related to their menstrual cycle. With great care oral contraceptives may be taken, as can hormones regulating hormone fluctuations which may 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 actions to take 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. Vomiting during pregnancy may be a sign that the disease has become active, and the colour of the urine should be monitored and a physician contacted as a precaution.
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 for people with acute intermittent porphyria.
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 suitability or unsuitability of drugs should always be carefully checked and an acute intermittent porphyria specialist consulted. Barbiturates, which are sometimes used in anaesthesia, must never be given. Sulphonamides must never be used to treat infections.
Surgical interventions should always be preceded by neurological and psychiatric evaluations in order to assess the risk of porphyria-related complications. Before an operation, glucose (sugar) can be administered in order to mitigate the effects of stress, fasting and drugs.
Treatment of an acute attack
During an attack the patient’s fluid balance, blood magnesium and sodium concentrations, should all be monitored. Daily controls which show rapid results 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 avoid complications.
A ten per cent glucose solution administered immediately at the onset of an attack will often halt it. Since this treatment generally has no effect on other medical conditions, it may be administered at an early stage.
Heme arginate therapy 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 levels to normalise and for pain to disappear. During the attack symptoms should be treated with appropriate medication. (See “Medication for Acute Porphyria” under the heading “Information material.”)
Abdominal pain may be so severe that morphine or other opiates are required. Tranquilisers, 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 the progression of the disease, even in the post-critical phase. Muscle function should be carefully monitored, as paralysis of the hands and feet may suddenly occur. Physiotherapy may be required.
Many people who have previously experienced attacks prefer to remain at home to deal with them themselves.
Regular check-ups
In order to prevent complications in the long term 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 55, a contrast-enhanced ultrasound examination should be carried out at least annually. 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 never experienced symptoms.
Personal medical information cards
When in contact with healthcare services, it is important that the person with PBGD deficiency is not prescribed unsuitable medication or treatment 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. 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 a duty physician 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 memorandum 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 a list of suitable and unsuitable medications.
Miscellaneous
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.
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 by increasing sugar intake, for example by consuming 4-6 sugar cubes an hour or drinking fruit juice. Swedish pharmacies sell a ready-to-drink glucose solution under the name of Nutrical. The recommended dose is two bottles a day for a maximum of four days. Over-consumption 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.
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 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 computer-based, national patient register organised by family.
Porphyria Clinic, Söder Hospital
Department of Internal Medicine, Söder Hospital, SE-118 83 Stockholm, Sweden. Tel +46 8ÿ616 10 00.
Porphyria Centre Sweden
Pauline Harper, MD, PhD, Porphyria Centre Sweden, CMMS, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 714 47, fax: +46 8 517 714 74, email: pauline.harper@karolinska.se.
Eliane Sardh, MD, PhD, Porphyria Centre Sweden, CMMS, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 714 43, fax: +46 8 517 714 74, email: elaine.sardh@ki.se.
Ylva Floderus, geneticist, PhD, Porphyria Centre Sweden, CMMS C2 71, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 714 52, fax: +46 8 517 714 74, email: ylva.floderus@karolinska.se.
Associate Professor Stig Thunell, Porphyria Centre Sweden, CMMS, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Email: stig.i.thunell@telia.com.
The Porphyria Clinic at the Söder Hospital
Eliane Sardh, MD, PhD, Department of Internal Medicine, Söder Hospital, SE-118 83 Stockholm, Sweden. Tel: +46 8 616 30 19, fax: +46 8 616 31 16, email: eliane.sardh@sodersjukhuset.se.
The Norrland Region
Associate Professor Christer Andersson, Project leader, 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) organises information meetings. Contact the Association for further information. (See under the heading, “Organizations for the disabled/patient associations etc.”)
RMP, The Swedish Porphyria Association, Porphyria Centre Sweden, Karolinska University Hospital, Huddinge M96, SE-141 86 Stockholm, Sweden. Tel: +46 8 711 56 09, fax: +46 8 585 827 60, email: porfyrisjukdomar@gmail.com, 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 federation of rare disease organizations, serving the interests of people with rare disorders.
The Porphyria Centre Sweden develops care programmes for porphyria. Currently (June 2010) some clinics in Sweden provide consultations and information with the support of the Porphyria Centre. (See under the heading “Resource personnel.”)
In collaboration with Porphyria Centres in Europe, research at the Porphyria Centre Sweden focuses mainly on improving the reliability of laboratory analyses and on gaining deeper knowledge of the disease by means of epidemiological studies. Work is 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 publication, “Patient’s and doctor’s guide to medication for acute porphyria 2005,” and “The Drug Database for Acute Porphyria.” (See under the heading “Information material.”)
An information leaflet on acute porphyria that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2010-4-22). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.
“Patient’s and doctor’s guide to medication for acute porphyria 2005.” English version, 12 euros. This publication 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, M96, SE-141 86 Stockholm, Sweden. Tel: +46 8 711 56 09, email: porfyrisjukdomar@gmail.com.
The Swedish Porphyria Association (RMP) publishes information for people with porphyria and healthcare professionals. See www.porfyri.se. The material below (in Swedish only) can be ordered from the Association’s office, tel: +46 8 711 56 09.
- Riksföreningen mot porfyrisjukdomar (RMP). Information about porphyria and how the patient association works.
- Kost vid akut porfyri. Information about suitable nutrition for carriers of acute porphyria.
Books (in Swedish only)
Andersson C, Harper P. Läkemedelsboken 2009-2010. Apoteket AB 2009; 900-908.
Andersson C, Harper P. Porfyri. Internmedicin. Berglund G, Engström-Laurent A, Lindgren S, Lindholm N. Stockholm, Liber AB 2006; 558-567.
Harper P. Porfyri, in: Endokrinologi, ed. Werner S. Liber AB, Stockholm 2004; 368-369.
Thunell S, Harper P. Porfyriner, in: Laurells klinisk kemi i praktisk medicin, eds. Nilsson-Ehle P, Ganrot P, Grubb A, Lindstedt G, Simonson P, Stenflo J et al. Studentlitteratur, Lund 2003; 623-631.
Databases
Porphyria Centre Sweden; consultations, investigations, referrals, testing. www.karolinska.se/porfyri.
The Scandinavian Drug Database for Acute Porphyria. (In English, Swedish and Norwegian.) The database lists suitable and unsuitable medication in cases of acute porphyria. Includes lists of medication to be avoided:
www.drugs-porphyria.org.
European Porphyria Initiative, EPI. European common initiative to provide information on porphyria.
www.porphyria-europe.com.
Andersson C, Bjersing L, Lithner F. The epidemiology of hepatocellular carcinoma in patients with acute intermittent porphyria. J Intern Med 1996; 240: 195-201.
Andersson C, Bjersing L, Lithner F. Akut intermittent porfyri ökar risken för levercancer. Tidig cancerdiagnos och varierad kirurgi kan förbättra prognosen. Läkartidningen 1998; 95: 3043-3044.
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, Floderus Y, Wikberg A, Lithner F. The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study. Scand J Clin Lab Invest 2000; 60: 643-648.
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.
Andersson, C. Försiktighet med p-piller vid porfyri. Läkartidningen 2004; 101: 2167.
Floderus Y, Harper P, Henrichson A, Thunell S. Porfyri - minering i metabolismen. Läkartidningen 1998; 95: 2932-2935.
Floderus Y, Harper P, Henrichson A, Thunell S, Andersson D. Bäst att förebygga vid akut intermittent porfyri. Läkartidningen 1998; 95: 3045-3050.
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, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10: 444-455.
Lithner F. Otillfredställande smärtbehandling vid attack av akut intermittent porfyri. Läkartidningen 2001; 98: 942-944.
Moore RM, Hift RJ. Drugs in the acute porphyrias - toxicogenetic diseases. Cell Mol Biol 1997; 43: 89-94.
Tenhunen R, Mustajoki P. Acute porphyria: treatment with heme. Semin Liver Dis 1998; 18: 53-55.
Thunell S. Porphyrins, porphyrin metabolism and porphyrias. I. Update. Scand J Clin Lab Invest 2000; 60: 509-540.
Thunell S. Porphyrins, porphyrin metabolism and porphyrias. II. Diagnosis and monitoring in the acute porphyrias. Scand H Clin Lab Invest 2000; 60: 541-546.
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.
Wikberg A, Andersson C, Lithner F. Neuropati i underben och fötter vid akut intermittent porfyri. Läkartidningen 2001; 98: 4038-4041.
OMIM (Online Mendelian Inheritance in Man).
www.ncbi.nlm.nih.gov/omim
search: acute intermittent porphyria
GeneReviews (University of Washington),
www.genetests.org (first select 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 draft of this information material were Associate Professor Folke Lithner, Norrlands University Hospital, Umeå, Sweden and Associate Professor Stig Thunell, Karolinska University Hospital, Huddinge, Stockholm.
The revision was carried out by Associate Professor Stig Thunell, Karolinska University Hospital, Huddinge, 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: 2010-11-11
Version: 2.2
Publication date of the Swedish version: 2010-06-16
For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.