THE DIAGNOSIS OF ACUTE HEPATIC PORPHYRIA BY PLASMA ALA, PBG, FLUORESCENCE SCANNING AND ENZYME ASSAYS, USING DNA ANALYSIS AS REFERENCE

J.H.P. Wilson, A. Edixhoven, R. Koole, F.W.M. de Rooij

Erasmus MC, Rotterdam, The Netherlands

Background: We have developed an enzymatic assay for plasma aminolevulinic acid (ALA) and porphobilinogen (PBG), which is a more sensitive test for acute intermittent porphyria (AIP) than urine ALA and PBG analysis. Plasma fluorescence scanning has been reported to be a more sensitive test for variegate porphyria (VP) than faeces analysis. To determine whether the combination of plasma ALA, PBG and fluorescence scanning could be used as a screening test for AIP, VP and hereditary coproporphyria (HCP), we assessed these assays in a large group of subjects characterized for AIP, VP and HCP at the DNA level.

Methods: We evaluated all patients with AIP, VP and HCP and their relatives for whom the genotype and a plasma ALA, PBG and fluorescence scan were available in our reference laboratory. In addition, hydroxymethylbilane synthase (HMBS), coproporphyrinogen oxidase (CPO) and protoporphyrinogen oxidase (PPOX) were determined in many subjects. No patients had acute porphyric complaints at analysis.

Results: Percentage with abnormal results and number of subjects tested in brackets.

Test

AIP

HCP

VP

Controls

Plasma ALA

83% (98)

56% (18)

65% (121)

12% (201)

Plasma PBG

89% (98)

56% (18)

57% (121)

3% (201)

Fluorescence

51% (88)

29% (21)

34% (121)

0% (201)

HMBS ery’s

89% (228)

0% (20)

0% (87)

0,5% (218)

CPO lympho’s

0% (11)

100% (24)*

7% (70)*

0% (97)

PPOX lympho’s

18% (11)

30% (24)*

87% (75)*

15% (81)

* One family had combined HCP and VP mutations.

All patients who had previously had an acute porphyric attack, had abnormal plasma ALA, PBG or fluorescence results in the asymptomatic period.

Conclusions: The combination of plasma ALA, PBG, fluorescence scanning will detect all patients with AIP, HCP or VP who have previously had an acute attack. These tests, combined with erythrocyte HMBS, can be performed on a single blood sample and will detect 100% of asymptomatic individuals with an AIP mutation. CPO assays in lymphoblastoid cells are very reliable for detecting HCP. Mutation analysis remains the only accurate method of confirming VP in asymptomatic individuals.