This enzyme deficiency can result in the accumulation of toxic porphyrin precursors in the body. However, the deficiency by itself is not sufficient to produce symptoms of the disease and most individuals with a HMBS gene mutation do not develop symptoms of AIP. Additional factors such as endocrine influences e. Most of these triggers are believed to stimulate increased heme production synthesis in the liver and include certain drugs, excessive alcohol consumption, fasting or dieting e. AIP is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for developing symptoms of the disorder.
|Published (Last):||14 June 2016|
|PDF File Size:||14.46 Mb|
|ePub File Size:||10.40 Mb|
|Price:||Free* [*Free Regsitration Required]|
Acute intermittent porphyria, which causes abdominal pain and neurologic symptoms, is the most common acute porphyria. Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms. See also Overview of Porphyrias. Acute intermittent porphyria occurs in people of all ethnic groups. In most countries, it is the most common of the acute porphyrias. Other acute porphyrias include.
Acute intermittent porphyria is due to a deficiency of the enzyme porphobilinogen deaminase also known as hydroxymethylbilane synthase that leads to accumulation of the porphyrin precursors delta-aminolevulinic acid and porphobilinogen initially in the liver. The disorder is inherited due to a single abnormal gene from one parent.
The normal gene from the other parent keeps the deficient enzyme at half-normal levels, which is sufficient to produce normal amounts of heme. Most people with a deficiency of porphobilinogen deaminase never develop symptoms. In some people, however, certain factors can precipitate symptoms, causing an attack. Factors that can cause an acute porphyria attack include. Many drugs including sex hormones, barbiturates, antiseizure drugs, and sulfonamide antibiotics. Usually a combination of factors is involved in causing an attack.
Sometimes the factors that cause an attack cannot be identified. Attacks are more common in women than in men and occur only very rarely before puberty. Very rarely, the disorder is inherited from both parents and therefore two abnormal genes are present. Symptoms may then appear in childhood and include developmental abnormalities. People with porphyria should discuss use of any drug, including nonprescription drugs, medicinal herbs, and supplements, with their doctors.
The website Porphyria Drugs may provide additional information. Many people never experience symptoms of acute intermittent porphyria. Other people may have only a few attacks over their lifetimes. However, some people have recurrent attacks.
Many people have pain or other symptoms between attacks. Symptoms occur as attacks that usually last a few days but occasionally longer. Such attacks usually first appear after puberty.
In some women, attacks develop during the second half of the menstrual cycle , likely triggered by the elevation of progesterone levels that occurs then. Abdominal pain is the most common symptom. The pain can be so severe that doctors may mistakenly think that abdominal surgery is needed. Other digestive symptoms include nausea, vomiting, severe constipation, or diarrhea rarely. Mental symptoms, such as irritability, restlessness, insomnia, agitation, tiredness, and depression, are common.
Nervous system symptoms are numerous. Nerves that control muscles can be affected, leading to weakness, usually beginning in the shoulders and arms. The weakness can progress to virtually all the muscles, including those involved in breathing. Tremors and seizures may develop.
Recovery from symptoms may occur within a few days, although complete recovery from severe muscle weakness may take several months or years. In some people, symptoms of lesser intensity, such as fatigue, headache, back or thigh pain, insomnia, depression, or anxiety, linger. Attacks are rarely fatal. However, in a few people, attacks are disabling. Long-term complications of acute intermittent porphyria may include persistent muscle weakness, high blood pressure , chronic kidney disease , cirrhosis , and liver tumors.
The severe digestive and neurologic symptoms of acute intermittent porphyria resemble symptoms of many more common disorders. Laboratory tests done on samples of urine taken during an attack show increased levels of two porphyrin precursors delta-aminolevulinic acid and porphobilinogen. Levels of these precursors are very high during attacks and remain high in people who have repeated attacks. The precursors can form porphyrins, which are reddish. These porphyrins turn the urine red to red-brown.
The color is especially evident after the urine specimen is exposed to light and air. Relatives without symptoms can be identified as carriers of the disorder by measuring porphobilinogen deaminase in red blood cells or, with greatest certainty, by DNA testing. Diagnosis before birth is also possible but usually is not needed because most affected people never get symptoms.
People who have attacks at predictable times, such as women whose attacks are related to the menstrual cycle, can be given heme by vein to prevent attacks. Premenstrual attacks in women can be prevented with one of the gonadotropin-releasing hormone agonists used to treat endometriosis , although this treatment should only be directed by doctors who are experts in treating porphyria.
People who have attacks of acute intermittent porphyria are often hospitalized for treatment of severe symptoms. People with severe attacks are treated with hemin given by vein.
Blood and urine levels of delta-aminolevulinic acid and porphobilinogen are promptly lowered and symptoms subside, usually within several days. If treatment is delayed, recovery takes longer, and some nerve damage may be permanent. Dextrose given by mouth or by vein if people are vomiting can also be beneficial, particularly in people whose attacks are brought on by a low-calorie, low-carbohydrate diet, but these measures are less effective than heme.
Nausea, vomiting, anxiety, and restlessness are treated with a phenothiazine-type drug for a short time. Ondansetron may also be given for nausea. Insomnia may be treated with chloral hydrate or low doses of a benzodiazepine but not a barbiturate. An overly full bladder may be treated by draining the urine with a catheter. Doctors ensure that people do not take any of the drugs known to precipitate an attack, and—if possible—address other factors that may have contributed to the attack.
Treatment of seizures is problematic, because almost any antiseizure drugs would worsen an attack. Levetiracetam appears to be safe to use. Beta-blockers may be used to treat rapid heart rate and high blood pressure. People with evidence of kidney damage are usually referred to a kidney specialist nephrologist.
Because the risk of liver cancer is high among people with acute intermittent porphyria, people who are older than 50 are screened for liver cancer at least once per year. Liver transplantation can cure acute intermittent porphyria. Doctors consider transplantation for people with poor quality of life and risk of permanent kidney or nervous system damage because of severe recurrent attacks. Some people may also need kidney transplantation.
From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world.
The Merck Manual was first published in as a service to the community. Learn more about our commitment to Global Medical Knowledge. This site complies with the HONcode standard for trustworthy health information: verify here. Common Health Topics. Commonly searched drugs. Ranitidine Withdrawn from US Market. Prevention of Acute Attacks. Treatment of acute attacks Other treatment. More Information. Test your knowledge. Elevated total cholesterol levels increase the risk for which of the following conditions?
More Content. Click here for the Professional Version. Many people never experience symptoms. Laboratory tests are done on urine samples taken during the attack. Maintaining good nutrition and avoiding alcohol and drugs that trigger attacks are important. Variegate porphyria. Delta-aminolevulinic acid dehydratase-deficiency porphyria, which is extremely rare. Variegate porphyria and hereditary coproporphyria may also cause skin cutaneous symptoms.
Exposure to organic solvents for example, in dry cleaning fluids or paints. Rapid heart rate. Most of these symptoms, including the digestive ones, result from effects on the nervous system. Irregular heart rhythm is a dangerous complication during an attack.
Urine tests. Attacks of acute intermittent porphyria can be prevented by. Maintaining good nutrition, including eating sufficient carbohydrates. Treatment of the acute attack is identical for all the acute porphyrias.
Heme given by vein. American Porphyria Foundation. European Porphyria Network.
Porphyria, Acute Intermittent
Acute intermittent porphyria, which causes abdominal pain and neurologic symptoms, is the most common acute porphyria. Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms. See also Overview of Porphyrias. Acute intermittent porphyria occurs in people of all ethnic groups. In most countries, it is the most common of the acute porphyrias.
Acute Intermittent Porphyria (AIP)
Acute intermittent porphyria AIP is a rare autosomal dominant metabolic disorder affecting the production of heme resulting from a deficiency of the porphobilinogen deaminase. It is the most common of the acute porphyrias. The clinical presentation of AIP is highly variable and non-specific. The patients are typically asymptomatic, with most gene carriers having no family history because the condition had remained latent for several generations. AIP is one of the four porphyrias that presents as an acute attack.
Acute Intermittent Porphyria
Recent mapping of acute intermittent porphyria AIP in Sweden has confirmed its very high prevalence in northern districts, though about fifty per cent of the gene carriers are to be found in the central and southern parts of the country. More than eighteen different AIP mutations are currently recognised in the Swedish kindreds. One mutations, evidently originating in northern Sweden, is predominant. As AIP is a pharmacogenetic disease, more than substances being currently known to precipitate the neuropsychiatric symptoms, the greatest care is required in prescribing drugs to carriers of genetic predisposition to the disease. Guidelines are provided in the booklet. Where doubt exists, specialists should be consulted since there are a number of factors that may contribute to an adverse reaction. Early diagnosis, preferably before puberty, and counselling are the cornerstones of management, and genetic analysis the diagnostic tool of choice, applicable in most families.
Acute Intermittent Porphyria Associated with Respiratory Failure: A Multidisciplinary Approach