Porphobilinogen Deaminase, Whole Blood

Levels are usually decreased by up to 50% in patients with acute intermittent porphyria. However, some patients may have values within the reference interval.

Not all persons with the genetic defect have a history of clinical disease.

Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that is characterized by deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD). 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.g. hormonal changes), the use of certain drugs, excess alcohol consumption, infections, and fasting or dietary changes are required to trigger the appearance of symptoms.

The PBGD enzyme deficiency is caused by a mutation in the HMBS gene which is inherited as an autosomal dominant trait (only one HMBS gene copy is affected). However, the majority of people with a mutation in this gene do not develop symptoms of AIP; additional factors, often called “triggers” are also required to cause symptomatic acute Porphyria. These factors are not necessarily the same for each individual, and susceptibility to specific triggers may vary during a patient’s lifetime. 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.g. caloric restriction), stress, infections or certain hormonal (endocrine) factors.

Signs and Symptoms:

AIP manifests after puberty, especially in women (due to hormonal influences). Symptoms usually come as discrete attacks that develop over two or more days. Abdominal pain, which is associated with nausea, can be severe and occurs in most cases.

Other symptoms may include:

• vomiting
• constipation
• pain in the back, arms and legs
• muscle weakness (due to effects on nerves supplying the muscles)
• urinary retention
• palpitations (due to a rapid heart rate and often accompanied by increased blood pressure)
• confusion, hallucinations and seizures
• insomnia

Sometimes the level of salt (sodium and chloride) in the blood decreases markedly and contributes to some of these symptoms. The skin is not affected in AIP.

AIP can be associated with a range of symptoms and physical findings that can potentially involve multiple organ systems of the body. The course and severity of attacks is highly variable from one person to another. In some cases, particularly those without proper diagnosis and treatment, the disorder can potentially cause life-threatening complications. It is important to note the highly variable nature of AIP and that affected individuals may not have all of the symptoms discussed above. Affected individuals and parents of affected children should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

The symptoms of AIP usually occur as episodes or “attacks” that develop over course of several hours or a few days. Affected individuals usually recover from an attack within days. However, if an acute attack is not diagnosed and treated promptly recovery can take much longer, even weeks or months. Most affected individuals do not exhibit any symptoms in between episodes. Onset of attacks usually occurs in the 20s or 30s but may occur at or just after puberty. Onset before puberty is extremely rare. Attacks are much more common in women than men, probably because of the menstrual cycle hormones. Approximately 3%-5% of affected individuals, predominately women, experience recurrent attacks, which are defined as more than 4 per year, for a period of many years.

Most people who inherit the gene for AIP never develop symptoms. However, experts recommend that all relatives of someone with AIP obtain testing, to determine who has the genetic trait and who does not. Those who test positive for the trait should be educated as to measures that will help avoid attacks. Prevention and avoidance of unsafe medications is essential to good management.

The Porphobilinogen Deaminase, Whole Blood test is used to a) confirm a diagnosis of acute intermittent porphyria (AIP) following a positive urine porphobilinogen (PBG) test and/or b) to evaluate disease risk in family members of an individual with a confirmed diagnosis of AIP.

Porphobilinogen deaminase, also known as uroporphyrinogen I synthase, is commonly confused with uroporphyrinogen III synthase, the enzyme deficient in congenital erythropoietic porphyria (CEP).

The porphyrias are a group of inherited disorders resulting from enzyme defects in the heme biosynthetic pathway. Acute intermittent porphyria (AIP) is caused by diminished erythrocyte activity of porphobilinogen deaminase (PBGD), also known as uroporphyrinogen I synthase or hydroxymethylbilane synthase (HMBS).

Onset of AIP typically occurs during puberty or later. Individuals may experience acute episodes of neuropathic symptoms.