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Acute Intermittent Porphyria

by Herbert L. Bonkovsky, MD, Vinaya Maddukuri, MD

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.

  • Laboratory tests are 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.

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, and the extremely rare delta-aminolevulinic acid dehydratase-deficiency porphyria. Some acute porphyrias also cause skin (cutaneous) symptoms.

People with acute intermittent porphyria first experience sudden onset of neurologic symptoms. Attacks are more common in women than in men and occur only very rarely before puberty.

Acute intermittent porphyria is due to a deficiency of the enzyme porphobilinogen deaminase (also known as hydroxymethylbilane synthase) that leads to accumulation of the heme 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. 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.

Most people with a deficiency of porphobilinogen deaminase never develop symptoms. In some people, however, certain factors can precipitate symptoms, causing an attack. Many drugs (including barbiturates, anticonvulsants, and sulfonamide antibiotics) can bring on an attack. Sex hormones, such as progesterone and related steroids, can precipitate symptoms, as can low-calorie and low-carbohydrate diets, ingestion of alcohol, and exposure to organic solvents (for example, in dry cleaning fluids or paints). Mental stress or an infection is sometimes implicated. Usually a combination of factors is involved. Sometimes the factors that cause an attack cannot be identified.

Some Drugs That May Cause an Attack of Acute Intermittent Porphyria*

Category/Disorder Treated

Examples

Anesthetics (local)

Lidocaine

Anticonvulsants

Barbiturates

Carbamazepine

Ethosuximide

Lamotrigine

Phenytoin

Valproate

Antihistamines

Clemastine

Dimenhydrinate

Hydroxyzine

Certain antihyperglycemic drugs (sulfonylureas)

Acetohexamide

Chlorpropamide

Glimepiride

Glipizide

Glyburide

Tolazamide

Tolbutamide

Antimicrobials

Chloramphenicol

Clindamycin

Erythromycin

Ketoconazole

Nitrofurantoin

Rifampin

Ritonavir

Sulfonamides

Trimethoprim

Heart drugs

Hydralazine

Lidocaine

Methyldopa

Nifedipine

Spironolactone

Hormones

Danazol

Progesterone

Synthetic progestins

Migraine drugs

Dihydroergotamine

Sedatives

Barbiturates

*Because different people with porphyria may react differently to drugs and because many drugs have not been tested in people with porphyria, this list is only for general guidance. People with porphyria should discuss use of any drug with their doctor.

Symptoms

Many people never experience symptoms. Symptoms occur as attacks usually lasting 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.

Abdominal pain is the most common symptom. The pain can be so severe that doctors may mistakenly think that abdominal surgery is needed. Gastrointestinal symptoms include nausea, vomiting, and constipation or diarrhea. The bladder may be affected, making urination difficult and sometimes resulting in an overly full bladder. Urine may be red or reddish brown. A rapid heart rate, high blood pressure, sweating, and restlessness are also common during attacks. Interference with sleep is typical. High blood pressure can continue after the attack. Mental symptoms are common, from irritation, restlessness, insomnia, and agitation to tiredness and depression.

Most of these symptoms, including the gastrointestinal ones, result from effects on the nervous system. 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. 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. Attacks are rarely fatal. However, in a few people, attacks are disabling.

Long-term complications of acute porphyria may include persistent muscle weakness, high blood pressure, kidney failure, cirrhosis, and liver tumors.

Diagnosis

The severe gastrointestinal and neurologic symptoms resemble those of many more common disorders. Laboratory tests done on samples of urine taken during an attack show increased levels of two heme 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.

Relatives without symptoms can be identified as carriers of the disorder by measuring porphobilinogen deaminase in red blood cells or sometimes by DNA testing. Diagnosis before birth is also possible but usually is not needed because most affected people never get symptoms.

Prevention

Attacks of acute intermittent porphyria can be prevented by

  • Maintaining good nutrition

  • Consuming a high-carbohydrate diet

  • Avoiding alcohol

  • Avoiding drugs that can cause an attack

  • 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 (see Endometriosis : Treatment of Endometriosis), although this treatment should only be directed by doctors who are experts in treating porphyria.

Treatment

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

Glucose 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 or low-carbohydrate diet, but these measures are less effective than heme. Pain can be controlled with drugs (such as opioids).

Nausea, vomiting, anxiety, and restlessness are treated with a phenothiazine-type drug for a short time. 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 anticonvulsant would worsen an attack. Beta-blockers may be used to treat rapid heart rate and high blood pressure.

Liver transplantation will cure the disorder. Doctors consider transplantation for people who are at risk of permanent kidney or nervous system damage because of severe recurrent attacks. Some people may also need kidney transplantation.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • CLEOCIN
  • FURADANTIN, MACROBID, MACRODANTIN
  • No US brand name
  • AMARYL
  • TAVIST-1
  • RIFADIN, RIMACTANE
  • DIABETA, GLYNASE
  • ERY-TAB, ERYTHROCIN
  • VISTARIL
  • XYLOCAINE
  • ALDACTONE
  • TEGRETOL
  • D.H.E. 45, MIGRANAL
  • No brand name
  • NORVIR
  • CRINONE
  • GLUCOTROL
  • DIABINESE
  • DILANTIN
  • NIZORAL
  • LAMICTAL
  • ZARONTIN
  • ADALAT CC, PROCARDIA