Acute porphyria: the cost of suspicion

Abstract

Porphyria refers to a group of diseases of the nervous system or skin (or both) that are associated with the generation of excess porphyrin intermediates or their precursors as a result of decreased enzymatic activity during heme synthesis ( 1 Moore M.R. McColl K.E. Fitzsimons E.J. Goldberg S.A. The porphyrias. Blood Rev. 1990; 4: 88-96 Abstract Full Text PDF PubMed Scopus (19) Google Scholar ). The disease is primarily hereditary, transmitted often by an autosomal dominant mechanism. The genetic defects show both reduced penetrance and variable expressivity ( 2 Elder G.H. Genetic defects in the porphyrias types and significance. Clin Dermatol. 1998; 16: 225-233 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ). The diagnosis of clinical porphyria requires the presence of both symptoms and signs and a measurable biochemical abnormality ( 3 Tefferi A. Solberg Jr, L.A. Ellefson R.D. Porphyrias clinical evaluation and interpretation of laboratory tests. Mayo Clin Proc. 1994; 69: 289-290 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar ). In contrast, asymptomatic persons with defective enzymatic activity are often carriers of a mutant allele and are considered to have “latent disease” ( 4 Pierach C.A. Weimer M.K. Cardinal R.A. et al. Red blood cell porphobilinogen deaminase in the evaluation of acute intermittent porphyria. JAMA. 1987; 257: 601 Crossref Scopus (29) Google Scholar , 5 Lundin G. Lee J.S. Thunell S. Anvret M. Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families. Hum Genet. 1997; 100: 63-66 Crossref PubMed Scopus (19) Google Scholar , 6 Nordmann Y. Puy H. Da Silva V. et al. Acute intermittent porphyria prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France. J Intern Med. 1997; 242: 213-217 Crossref PubMed Scopus (100) Google Scholar ). Therefore, neither the detection of excess tissue porphyrins nor the demonstration of reduced enzyme activity is specific for clinically overt disease.