101 Acute Hepatic Porphyrias 1 of 3

AIP, HCP, VP & ADP

Please note that the symptoms and treatments for AIP are applicable to Variegate Porphyria (VP), Hereditary Coproporphyria (HCP), and ALAD Porphyria (ADP). Unlike AIP and ADP patients, however, VP and HCP patients often develop photosensitivity.

Acute Intermittent Porphyria (AIP) is a rare disease that is usually inherited from one parent. It is almost always latent (i.e. does not produce illness) in childhood and is usually latent in adults throughout life. When the disorder is active, it can cause intermittent attacks of abdominal pain as well as a variety of symptoms, which range from mild to life-threatening.

After the correct diagnosis of AIP is made, simple precautions can be taken to prevent attacks. It is important to check all relatives of Porphyria patients for the genetic defect, so they can take the same precautions and avoid becoming ill from Porphyria. Even relatives who have never had symptoms should be tested, as described below.

Diagnosis

Laboratory tests are the keystone of diagnosis in AIP. Because signs and symptoms are nonspecific, test samples should be handled with care and sent to a laboratory of excellence for testing and subsequent evaluation. A laboratory overseen by a Porphyria specialist would be the best choice.

Blood tests

The enzyme porphobilinogen deaminase (PBG-D) is abnormally low in the liver and in most other tissues of a patient with Acute Intermittent Porphyria. This is true whether or not the patient has clinical symptoms or biochemical activity of the disease. Activity of this enzyme can be measured fairly easily in red blood cells. This is a useful test, particularly for evaluation of relatives of previously diagnosed patients with known low levels of PBG-D. This enzyme was formerly known as uroporphyrinogen-1-synthase (URO-S), a term still used by some laboratories.

However, there are some practical difficulties with the red cell assay:

• In about 10% of patients and families, there is no decrease in activity of this enzyme, because the enzyme in red blood cells is slightly different from that in liver and most other tissues. Such patients and families have a defective enzyme expressed only in liver and other tissues, not in their red blood cells.
• Even when the enzymatic defect is expressed in red blood cells, about 10% of patients' values fall into a zone that overlaps with that of the normal population. This is referred to as the "indeterminate zone".
• Care must be exercised in the handling and storage of blood samples for testing. Although the PBG-D enzyme is relatively stable, activity will fall if samples are not refrigerated promptly and kept frozen until the time of assay.

Urine tests

Urine may appear purple during  an attack or after standing in the light

The amount of porphobilinogen (PBG) in urine is increased during attacks of AIP. PBG is a porphyrin precursor, not a porphyrin. The Watson-Schwartz test or the Hoesch test is used in many hospital laboratories as a qualitative test of the urine to determine whether there is an increased amount of PBG. The result is reported as "positive" or "negative", but the actual amount of PBG is not measured. Measuring the amount of PBG in a 24-hour specimen or even a spot sample of urine is a much better test. A very high urine PBG, when determined by a reliable method such as the Mauzerall-Granick method, is diagnostic for the presence of an acute Porphyria.

There are three acute porphyrias that can cause increases in PBG, namely AIP, Hereditary Coproporphyria (HCP) and Variegate Porphyria (VP). Acute attacks can occur in all of these conditions. Skin photosensitivity can occur in HCP and VP, but not AIP.

There are several considerations to keep in mind regarding PBG measurements:

• Urine PBG usually remains high between attacks of AIP, especially if the attacks are frequent. Thus, although a high PBG does indicate that the patient has an acute Porphyria, it does not prove that the patient is having an attack at the time.
• Urine PBG may gradually become normal if there have been no attacks of AIP for a long time.
• Urine PBG can become normal within 1-2 days after heme therapy.
• In patients with HCP or VP, urine PBG can become normal more quickly after attacks than in patients with AIP. Urine porphyrins usually stay increased in these patients even when the PBG falls to normal.
• Urine PBG is normal in most individuals who have inherited AIP but have never had symptoms. Therefore, it is not reliable for testing relatives.

Urine porphyrins are usually increased in acute porphyrias, but measuring them is less useful than measuring PBG. Increases in urine porphyrins are common in other medical conditions. Therefore, finding an increase in urine porphyrins may not mean that the patient has Porphyria.