Acute Intermittent Porphyria

Acute Intermittent Porphyria Definition

Acute Intermittent Porphyria (AIP) is a form of hereditary hepatic Porphyria. There are various types of Porphyria that affects people all around the world and AIP is one such form of the condition. This rare metabolic disorder is inherited in the autosomal dominant pattern and affects the production of heme in the body. One of its principal characteristics is the deficiency of the enzyme called porphobilinogen deaminase or PBGD (also known as hydroxymethylbilane synthase or HMB-synthase). Patients suffering from AIP are more at risk of suffering from serious conditions like liver cancer and renal failure.

Acute Intermittent Porphyria Synonyms

It can also be referred to by the following names:

Picture of Acute Intermittent Porphyria

Picture 1 – Acute Intermittent Porphyria

  • Swedish Type Porphyria
  • Pyrroloporphyria
  • Porphobilinogen Deaminase Deficiency
  • PBGD Deficiency
  • Uroporphyrinogen Synthase Deficiency

Acute Intermittent Porphyria Incidence

According to various researches, 1 out of every 10,000 people in United States suffers from AIP. It is known to occur more commonly in Sweden. However, this statistic is likely to be underestimated as only 10 to 15% individuals carrying the abnormal gene develop the symptoms. Females are at a slightly greater risk of developing this disease as compared to males.

Acute Intermittent Porphyria Causes

It is mainly caused by a mutation in the gene PBGD which results in decreased production of the enzyme Porphobilinogen deaminase. A reduced amount of PBGD hampers the production of heme (the oxygen-binding prosthetic group of hemoglobin), which sets off the condition. Mutation in the gene leading to reduced activity of all the enzyme molecules is another possible cause. The chances of developing the symptoms often depend on the location of the mutation within the gene. Certain mutations in the gene PBGD are more likely to bring about severe forms of the ailment.

Other factors like drugs, dietary changes and hormones also contribute to the occurrence of the mutation. In some cases, it is not possible to identify the exact activating factors behind the genetic mutation.

Acute attacks are often triggered by various medications, including:

  • Sulfonamide antibiotics
  • Barbiturates
  • Metoclopramide
  • Rifampin
  • Anti-seizure drugs

Individuals carrying the defective gene should avoid these medicines. Certain drugs are absolutely contraindicated in AIP due to their capability of inducing an attack. Alcohol intake and cigarette smoking are also counted among the risk factors. Reducing the amount of food intake for the purpose of weight loss as well as surgery, infections, depression and stress may also provoke attacks.

Endogenous hormones are known to be responsible for aggravating the symptoms, which may be one of the reasons for the attacks being more prevalent in women during later part (luteal phase) of menstrual cycle.

Acute Intermittent Porphyria Pathophysiology

The process of heme production in the human body consists of eight steps. The enzyme PBGD is responsible for controlling the third of these eight stages. Approximately 50% of the regular activity of the enzyme is lost due to the mutation in the gene PBGD. Under normal circumstances, the remaining 50% of PBGD activity is sufficient for producing the required amount of heme and does not cause any sign of enzyme deficiency. Sometimes, however, the body needs to accelerate the heme production due to some metabolic requirements. The defect in the third stage often makes it impossible to make as much heme as needed to meet the increased demands. Under these circumstances, porphobilinogen or PBG and aminolaevulinic acid or ALA (two other substances involved in the production of heme) begin piling up in the body. This accumulation leads to various AIP symptoms, such as abnormal urine color, possibly because of the actions of ALA on the nervous system of the patient.

Acute Intermittent Porphyria Inheritance

AIP follows the autosomal dominant inheritance pattern, meaning that inheriting one copy of the mutated gene from either parent is sufficient for causing the condition. Individuals carrying the abnormal gene responsible for causing this form of Porphyria have 50% chances of having a child with the disease.

Many people carrying the mutated gene do not develop the symptoms their whole lives. These people are the carriers of the defective gene and may pass it on to their children who may experience severe AIP attacks. Children born to a parent having the severe form of the disorder is more likely to develop the serious symptoms of AIP compared to those born to a parent who is only a carrier of the abnormality.

Acute Intermittent Porphyria Symptoms

The attacks of AIP are characterized by three major symptoms:

  • Abdominal pain or cramping
  • Light sensitivity causing blistering, rashes and Photodermatitis (scarring of skin)
  • Various muscle and nervous system problems including seizures, nerve damage and mental disturbances

Patients may experience a sudden attack which begins with severe abdominal pain, vomiting and constipation. Exposure to the sun during the attack can result in painful rashes and swelling along with reddening of the skin. The blisters resolve very slowly and may result in scarring as well as skin color change. The urine may become brown or red following an attack. In some instances, the urine can also turn deep purple or blue.

Other possible symptoms include:

  • Muscle pain
  • Pain in the legs and arms
  • Muscle weakness or even paralysis
  • Back pain
  • Joint pain
  • Migraine and headache
  • Fatigue
  • Numbness or tingling
  • Personality changes

In some instances, AIP can cause fatal attacks which can lead to life threatening symptoms like:

  • Extremely low blood pressure
  • Shock
  • Severe electrolyte imbalances

AIP may also cause various psychiatric or mental symptoms such as depression and anxiety.

Acute Intermittent Porphyria Prevention

It is not possible to prevent the inheritance of the defective gene if one or both parents are carrying it. However, gene reviews, genetic testing and parental screening may be useful for understanding the chances of having a child with AIP, especially in case of those who do not have the symptoms but are only carrying the mutation.

Individuals with the defective gene can take some measures in order to avoid the occurrence of the symptoms and attacks. It is important to understand the triggers and risk factors of the attacks to prevent them. One can avoid the attacks by staying away from the potential triggers of the attacks such as stress, certain medications, alcohol and fasting.

Prevention by Hormone Therapy

In women, the occurrence of the attack is sometimes associated with their menstrual cycle. In such cases, the patients may use birth control pills as these may prevent the attacks by controlling hormone fluctuation. However, this type of treatment should be performed with great care under proper supervision of a gynecologist and a Porphyria specialist

Acute Intermittent Porphyria Diagnosis

The diagnosis of AIP generally begins with a complete physical examination during which the doctor studies a patient thoroughly to detect any sign of the condition. The patient may be asked detailed questions regarding his or her symptoms. The physical exam may show an abnormality in the functioning of the deep tendon reflexes of the patient.

Blood and urine tests are performed to check whether there are any kidney problems and other irregularities. Various special tests are available for measuring the porphyrin levels in the blood. DNA testing is one of the most useful diagnostic exams to determine the form of Porphyria present in the patient by identifying the specific type and location of mutation in the responsible gene. Currently, the DNA testing can be done for diagnosing AIP only through certain research laboratories.

It is advisable to perform biochemical testing in before doing the DNA testing. The biochemical testing includes measuring the level of PBG in the urine and stool. Other exams used for detecting AIP include:

  • Testing of blood gases
  • Comprehensive metabolic panel
  • Abdominal ultrasound
  • Liver function tests like sulfobromophthalein retention test

Acute Intermittent Porphyria Differential Diagnosis

The attacks of AIP are often mistaken for other abdominal conditions that give rise to similar symptoms. It is important to rule out the possibility of the following disorders when diagnosing AIP:

  • Appendicitis
  • Adrenal Crisis
  • Bile Duct Tumors
  • Biliary Trauma
  • Acute Mesenteric Ischemia
  • Nephrolithiasis
  • Irritable Bowel Syndrome
  • Factitious Disorder
  • Portal Vein Obstruction
  • Biliary Disease
  • Cholelithiasis
  • Aortic Dissection
  • Diverticulitis
  • Abdominal Abscess
  • Choledocholithiasis
  • Constipation
  • Emphysema
  • Abdominal Hernias
  • Colonic Obstruction
  • Gallbladder Empyema
  • Emphysematous Pyelonephritis
  • Chronic Pelvic Pain
  • Amebic Hepatic Abscesses
  • Adrenal Carcinoma
  • Emphysematous Cholecystitis
  • Abdominal Angina
  • Gastric Outlet Obstruction
  • Cholecystitis
  • Endometriosis
  • Esophagitis
  • Fibromyalgia
  • Acute Gastritis
  • Intestinal Pseudo-obstruction
  • Hypertension
  • Intestinal Motility Disorders
  • Bile Duct Strictures
  • Ileus
  • Lead Nephropathy
  • Biliary Obstruction
  • Mediterranean fever (Familial)
  • Biliary Colic
  • Nerve Entrapment Syndromes
  • Ovarian Cysts
  • Acute Pancreatitis
  • Chronic Pancreatitis
  • Pelvic Inflammatory Disease
  • Chester Porphyria
  • Acute Pyelonephritis
  • Chronic Pyelonephritis
  • Lead Toxicity

Acute Intermittent Porphyria Treatment and Management

Avoiding the trigger factors can help an AIP patient to prevent acute attacks. However, these attacks may still occur when no apparent precipitating factor is present. Naturally, it is important to have a clear idea about the ways of managing the symptoms of an attack. The approach for treatment may vary depending on the signs as the main objective of treating AIP is managing the symptoms by increasing the level of heme.

Treating an Acute Attack

It is important to monitor the balance of fluids and the concentrations of sodium and magnesium in the blood of patients. Doctors should perform daily tests for this purpose until the symptoms of the attack subside because the concentrations of magnesium and sodium can drop suddenly to life-endangering levels during an attack. If required, proper supplements should be prescribed and administered intravenously for avoiding complications.

The progress of the attacks may often be halted by administering a 10 percent glucose solution immediately when the onset of the symptoms occurs. This treatment usually does not have any effect on other medical conditions and is applicable at the stage of onset.

An even more effective treatment option is the heme arginate therapy, which is also administered at the onset of an attack. The administration of heme arginate is performed intravenously in a 20 percent albumin solution. Generally, the porphyrin levels take 2 to 6 days to become normal. The pain slowly subsides with the normalization of the porphyrin levels.

In some cases, a doctor may prescribe opiates like morphine for controlling severe abdominal pain. Sleeping pills and tranquilizers along with proper rest in a calm environment may also help to cure the pain. The symptoms of nausea and vomiting may also be treated with proper medication. Beta blockers are useful for lowering the blood pressure and stabilizing the heart rate of the patient. Experts have suggested cimetidine (Tagamet) as an effective treatment option for the condition.

The PBG levels in the urine can indicate the degree of progression of the disorder, even after the critical phase passes away. It is important to monitor the muscle functioning of the patient as AIP may suddenly cause paralysis of the feet and hands. Physiotherapy and exercise may be helpful for fighting the condition. According to some researches, folic acid can be both clinically and biochemically beneficial for individuals suffering from AIP.

Treatment by Surgery

Extremely severe cases of this Porphyria may require surgical intervention. Sometimes, it leads to serious conditions like liver cancer, kidney damage and renal failure. In these cases, a doctor may recommend surgical procedures such as kidney or liver transplant. However, surgical treatment is not used unless the condition reaches an advanced stage where all the other treatment procedures fail to cure it.

Acute Intermittent Porphyria Prognosis

Early diagnosis and prompt treatment of the disease generally yields a positive outcome. The condition has a very low mortality rate as proper treatment helps patients recover completely from the attacks. However, individuals with chronic AIP often experience recurring attacks even when they take all the precautionary measures. Early treatment cures the severe symptoms and allows sufferers to live a relatively normal life.

Acute Intermittent Porphyria Diet and Nutrition

Individuals with the disorder should follow a high carbohydrate diet throughout their lives. It is not recommended to restrict or greatly lower their carbohydrate and calorie intake even for a short time because this may trigger the attack. A patient should consult a physician and/or a dietician if he or she experiences extreme weight gain and wishes to lose some body mass. However, fasting is never advisable for the weight loss of patients. Eating plenty of iron-rich food is also important. Otherwise, patients may suffer from iron deficiency and anemia. One should also avoid the foods that may work as a trigger for the attacks.

Acute Intermittent Porphyria Complications

The possible complications of AIP include the following:

  • Gallstones
  • Coma
  • Paralysis
  • Scarring of the skin
  • Respiratory failure (because of weak chest muscles)

Acute Intermittent Porphyria and Pregnancy

Pregnancy is not complicated by this disorder as patients and carriers have been proved to have a better pregnancy tolerance than what was formerly believed. An unborn child has approximately 50% risk of being born with the congenital disease. However, AIP is often associated with a higher risk of miscarriage.

Acute Intermittent Porphyria Support Groups

A number of forums and foundations provide information regarding the preventive measures along with proper treatment guidelines for spreading awareness about this type of Porphyria among the general public. These support groups include:

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Picture 2 – Acute Intermittent Porphyria Image

American Porphyria Foundation

4900 Woodway, Suite 780

Houston, Texas 77056-1837

Tel: (866)273-3635

Fax: (713)840-9552

Email: porphyrus@aol.com

Website: http://www.porphyriafoundation.com

MedicAlert Foundation International

2323 Colorado Avenue

Turlock, California 95382

United States of America

Tel: (888)633-4298

Fax: (209)669-2456

Email: Inquiries@medicalert.org

Website: http://www.medicalert.org

Children Living with Inherited Metabolic Diseases (CLIMB)

Climb Building

176 Nantwich Road

Crewe, Intl CW2 6BG

United Kingdom

Tel: 0845 241 2174

Email: info.svcs@climb.org.uk

Website: http://www.CLIMB.org.uk

Acute Intermittent Porphyria is a serious and potentially life threatening disease requiring early treatment for its patients to live a normal and healthy life. Carriers of the gene mutation responsible for AIP should have a thorough knowledge about the symptoms and basic treatment options in order to survive a sudden attack.