Porphobilinogen Deaminase (PBGD), Whole Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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. 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. Crises may be precipitated by a broad range of medications (including barbiturates and sulfa drugs), alcohol, infection, starvation, heavy metals, and hormonal changes. 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. More than 80% of individuals with deficiency mutation in the HMBS gene remain asymptomatic throughout their lives.
The biochemical diagnosis of AIP is made by demonstrating increased urinary excretion of porphobilinogen (PBG) and is most accurate during an acute episode. In addition, the diagnosis of AIP can be confirmed through the measurement of porphobilinogen deaminase (PBGD) enzyme activity in erythrocytes, although 5% to 10% of affected individuals exhibit normal erythrocyte PBGD activity. In addition, molecular genetic confirmation (HMBSS / HMBS Gene, Full Gene Analysis) is available on a clinical basis and can be particularly helpful in identifying asymptomatic family members at risk of acute symptoms.
The workup of patients with a suspected porphyria is most effective when following a stepwise approach. See Porphyria (Acute) Testing Algorithm in Special Instructions or contact Mayo Medical Laboratories to discuss testing strategies.
Confirmation of a diagnosis of acute intermittent porphyria (AIP)
Abnormal results are reported with a detailed interpretation that may include an overview of the results and their significance, a correlation to available clinical information provided with the specimen, differential diagnosis, recommendations for additional testing when indicated and available, and a phone number to reach a laboratory director in case the referring physician has additional questions.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Abstinence from alcohol for at least 24 hours prior to specimen collection is essential as ethanol induces porphobilinogen deaminase (PBGD) activity, which may lead to a 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. Additionally, enzyme activity may be increased during an acute attack, therefore, the enzyme level should be assessed when the patient is asymptomatic.
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