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Acute Intermittent Porphyria

By

Herbert L. Bonkovsky

, MD, Wake Forest University School of Medicine;


Sean R. Rudnick

, MD, Wake Forest University School of Medicine

Last full review/revision Dec 2020| Content last modified Dec 2020
Click here for the Professional Version
Topic Resources

Acute intermittent porphyria, which causes abdominal pain and neurologic symptoms, is the most common acute porphyria.

  • Many people never experience symptoms.

  • Symptoms may include vomiting, abdominal or back pain, weakness in arms or legs, and mental symptoms.

  • The most common symptom is generalized abdominal pain that lasts for several hours to days.

  • Laboratory tests are best done on urine samples taken during the attack.

  • Maintaining good nutrition and avoiding alcohol and drugs that trigger attacks are important.

  • Attacks are treated by giving glucose and sometimes heme.

  • Givosiran, a newer drug, decreases the number and severity of acute attacks.

Porphyrias are a group of disorders caused by deficiencies of enzymes involved in the production of heme. Heme is a chemical compound that contains iron and gives blood its red color. Heme is a key component of several important proteins in the body. (See also Overview of Porphyrias Overview of Porphyrias Porphyrias are a group of disorders caused by deficiencies of enzymes involved in the production of heme. Heme is a chemical compound that contains iron and gives blood its red color. Heme is... read more .)

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

  • Variegate porphyria

  • Hereditary coproporphyria

  • Delta-aminolevulinic acid dehydratase-deficiency porphyria, which is extremely rare

Variegate porphyria and hereditary coproporphyria may also cause skin (cutaneous) symptoms.

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.

Acute intermittent porphyria 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)

  • Hormonal changes in women

  • Low-calorie, low-carbohydrate diet

  • Ingestion of alcohol

  • Exposure to organic solvents (for example, in dry cleaning fluids or paints)

  • Emotional stress

  • Infection and other illnesses

  • Surgery

  • Smoking

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.

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Symptoms of Acute Intermittent Porphyria

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 Menstrual Cycle Menstruation is the shedding of the lining of the uterus (endometrium) accompanied by bleeding. It occurs in approximately monthly cycles throughout a woman's reproductive life, except during... read more , likely triggered by the elevation of progesterone levels that occurs then.

Abdominal pain that lasts for hours to days 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.

Other common symptoms include

  • Rapid heart rate

  • Elevated blood pressure

  • Sweating

  • Restlessness

  • Difficulty sleeping

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.

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.

Diagnosis of Acute Intermittent Porphyria

  • Urine tests

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 the level of the deficient enzyme 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.

Prevention of Acute Attacks

Attacks of acute intermittent porphyria can be prevented by

  • Maintaining good nutrition, including eating sufficient carbohydrates

  • Avoiding alcohol

  • Avoiding drugs that can cause an attack

  • Avoiding smoking

  • Avoiding physical and emotional stress and exhaustion

  • Avoiding crash diets to lose weight rapidly

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 Treatment In endometriosis, patches of endometrial tissue—normally occurring only in the lining of the uterus (endometrium)—appear outside the uterus. Why endometrial tissue appears outside the uterus... read more Treatment , although this treatment should only be directed by doctors who are experts in treating porphyria.

Givosiran, a newer drug, is sometimes given once per month by injection under the skin to prevent acute attacks.

Treatment of Acute Intermittent Porphyria

Treatment of the acute attack is identical for all the acute porphyrias.

  • Heme given by vein

  • Dextrose

People who have attacks of acute intermittent porphyria are often hospitalized for treatment of severe symptoms.

Treatment of acute attacks

People with severe attacks are treated with heme 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.

Pain can be controlled with drugs (such as acetaminophen and opioids).

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 many commonly used 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.

Other treatment

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.

More Information

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • American Porphyria Foundation: Aims to educate and support patients and families affected by porphyrias

  • American Porphyria Foundation: Safe/Unsafe Drug Database: Provides an up-to-date list of drugs available in the United States to assist physicians in prescribing for patients with porphyrias

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