Porphobilinogen Deaminase (PBGD), Whole Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Acute intermittent porphyria (AIP) is caused by diminished erythrocyte activity of porphobilinogen deaminase (PBGD), also known as uroporphyrinogen I synthase or hydroxymethylbilane synthase. Onset of AIP typically occurs during puberty or later. Individuals may experience acute episodes of neuropathic symptoms. Common symptoms include severe abdominal pain, peripheral neuropathy, and psychiatric symptoms. A broad range of medications (including barbiturates and sulfa drugs), alcohol, infection, starvation, heavy metals, and hormonal changes may precipitate crises. AIP is inherited in an autosomal dominant manner. At-risk family members of patients with a biochemical diagnosis of AIP should undergo appropriate testing. Timely diagnosis is important as acute episodes of AIP can be fatal. Treatment of AIP includes the prevention of symptoms through avoidance of precipitating factors. Fortunately, >80% of individuals with PBGD deficiency remain clinically unaffected throughout their lives.
The biochemical diagnosis of AIP is made during an acute episode by demonstrating increased urinary excretion of PBG, the substrate of PBGD. During asymptomatic periods, urinary PBG may be informative; however, a normal or only slightly increased result should be repeated during a subsequent crisis. In addition, the diagnosis of AIP can be facilitated through the measurement of PBGD enzyme activity in erythrocytes, though 5% to 10% of affected individuals exhibit normal erythrocyte PBGD activity.
For additional information on the recommended order of testing, the following algorithms are available in Special Instructions:
-Porphyria (Acute) Testing Algorithm
-Porphyria (Cutaneous) Testing Algorithm
For additional information regarding porphyrias, see The Heme Biosynthetic Pathway in Special Instructions.
Confirmation of a diagnosis of acute intermittent porphyria (AIP)
Diagnosis of AIP during latent periods
Acute intermittent porphyria (AIP) is 1 of the very few diseases where a single laboratory test can be diagnostic (porphobilinogen deaminase levels <6.0 nmol/sec/L are considered diagnostic for AIP). However, because AIP management requires a highly restricted lifestyle, we strongly encourage a second specimen to confirm abnormal results.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Porphobilinogen deaminase (PBGD), also known as uroporphyrinogen I synthase, is commonly confused with uroporphyrinogen III synthase, the enzyme deficient in congenital erythropoietic porphyria (CEP). For these cases, order UPGC / Uroporphyrinogen III Synthase (Co-Synthase) (Upg III S), Erythrocytes.
Abstinence from alcohol for at least 24 hours prior to specimen collection is essential as ethanol induces PBGD activity which may lead to false-normal result.
A normal result does not rule out acute intermittent porphyria; 5% to 10% of affected individuals will have normal erythrocyte PBGD activity.
False-positive values may result from enzyme degradation due to improper specimen handling. It is essential to adhere to instructions outlined in Specimen Required and Specimen Stability Information.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Reference ranges have not been established for patients who are <16 years of age.
> or =7.0 nmol/L/sec
6.0-6.9 nmol/L/sec (indeterminate)
<6.0 nmol/L/sec (diminished)
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Tortorelli S, Kloke K, Raymond K: Chapter 15: Disorders of porphyrin metabolism. In Biochemical and Molecular Basis of Pediatric Disease. Fourth edition. Edited by DJ Dietzen, MJ Bennett, ECC Wong. AACC Press 2010, pp 307-324
2. Nuttall KL, Klee GG: Analytes of hemoglobin metabolism - porphyrins, iron, and bilirubin. In Tietz Textbook of Clinical Chemistry. Fifth edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 2001, pp 584-607
3. Anderson KE, Sassa S, Bishop DF, Desnick RJ: Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill BookCompany, 2001, pp 2991-3062