​Porphyrias are hereditary metabolic diseases caused by a defect in a specific enzyme of the heme synthesis pathway. Diagnosis and monitoring of acute hepatic porphyrias (AHP), which result in neurovisceral crises, are routinely performed by quantifying delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine using a manual ion exchange chromatography (IEC) method. However, this method requires a great deal of time and personnel, and is limited to urine analysis.

In this work, the authors used a new liquid chromatography-mass spectrometry (LC-MS) method that enabled rapid, simple quantification of ALA and PBG in 2,260 urine samples and 309 blood samples collected during two years of routine laboratory activity. The results were compared with those obtained using IEC for urine, and plasma concentrations were measured in healthy subjects and subgroups of symptomatic and asymptomatic AHP subjects. In urine, clinical decision limits were not affected by the change in method. Two-thirds of asymptomatic AHP carriers had increased urine PBG concentrations, and urine and plasma concentrations correlated well, except in patients with renal disease.

The LC-MS-based method for routine diagnosis and follow-up of acute hepatic porphyrias detects more asymptomatic carriers than the historical method. Blood analysis is particularly relevant for patients with renal disease, as urine measurements underestimate the increase in levels of the two biomarkers, ALA and PBG.

Contact : Thibaud Lefebvre (thibaud.lefebvre@aphp.fr ou thibaud.lefebvre@cea.fr)

Legend: Installation of a chromatography column on the mass spectrometer © F. Rhodes/CEA