Table 1.

Biochemical Characteristics of Clinically Manifest AIP

Enzyme DefectEnzyme ActivityErythrocytesUrineStoolPlasma
Hydroxymethylbilane synthase (HMBS) (EC 2.5.1.61)HMBS ~50% of normal 1, 2Erythrocyte porphyrins: normalPBG 3 and ALA 4: increased
Porphyrins: increased 5
Total porphyrin: normal or small increase 6 Coproporphyrin isomer III/I ratio: normal 7Plasma porphyrins: increased fluorescence emission peak ~619 nm 8
1.

Activity is decreased in all tissues, except in the 3% of individuals with the non-erythroid variant of AIP in which erythrocyte HMBS activity is normal.

2.

Measurement of erythrocyte HMBS activity is not required for the diagnosis of an acute attack of AIP. Mean erythrocyte HMBS activity is 50% of normal but overlap between AIP and reference ranges diminishes its sensitivity and specificity as a diagnostic test for AIP, even when persons with the non-erythroid variant are excluded [Kauppinen & Fraunberg 2002].

3.

PBG (porphobilinogen) is increased more than ALA (5-aminolevulinic acid). A normal PBG concentration in a symptomatic individual excludes the diagnosis of AIP. PBG concentrations decrease during remission but may remain increased for months or years.

4.

ALA is often measured with PBG by specialist laboratories but does not appear to provide any significant additional diagnostic information in uncomplicated AIP (see Differential Diagnosis).

5.

Increase mainly indicates in vitro condensation of PBG to uroporphyrins. Total urinary porphyrin, but not PBG, concentration may be increased in various disorders, including alcohol abuse and liver disease [Badminton et al 2012].

6.

The increase may be large if an analytic method that includes ether-insoluble porphyrins, e.g., uroporphyrin, is used [Rossi 1999].

7.

Excludes hereditary coproporphyria (see Differential Diagnosis)

8.

Plasma porphyrin concentration is usually increased during an acute attack. Plasma porphyrin fluorescence emission scanning excludes variegate porphyria if the peak is at less than 622 nm (see Differential Diagnosis).

From: Acute Intermittent Porphyria

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Ardinger HH, Pagon RA, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2018.
Copyright © 1993-2018, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2018 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.