Dual porphyrias revisited

Abstract

The porphyrias are clinically and genetically heterogeneous metabolic diseases, which predominantly result from a hereditary dysfunction in the pathway of haeme biosynthesis. Currently, at least eight different forms of porphyrias can be differentiated, all of them characterized by a specific enzyme deficiency that is either inherited in an autosomal-dominant fashion, autosomal recessively or, in the case of porphyria cutanea tarda, might also be acquired. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Traditionally, the diagnosis of porphyria is made on the basis of clinical symptoms, characteristic biochemical findings and enzyme assays. In some porphyria patients and families, however, these diagnostic tools can reveal simultaneous findings compatible with two different forms of porphyria, a phenomenon referred to as dual porphyria. Here, we give an overview on what is currently known about these peculiar variants of porphyria and suggest that, whenever feasible, molecular genetic analysis should complement the analytical techniques used to characterize patients and families in which a double enzymatic deficiency within the haeme biosynthetic pathway is assumed.

Lessons learned from DNA repair defective syndromes

“…The establishment of centers of excellence for studying the whole variety of rare genetic syndromes with DNA repair defects may be very helpful in this direction. This would parallel other genetic diseases like ichthyoses (145) or porphyrias (146,147) where specialized centres were very helpful, especially with respect to molecular‐genetic laboratory diagnostics.…”

Clinical and Laboratory Diagnosis of the Porphyrias

“…[30][31][32][33][34][35][36] Cases termed dual porphyria have genetic alterations of two heme pathway enzymes, which can be suspected based on unusual combinations of biochemical features and then confirmed by DNA studies for identification of dual mutations. [37][38][39] …”

“…39 Only a few cases have been fully documented at the molecular level. For example, a male with symptoms of acute porphyria was heterozygous for a CPOX and ALAD mutations; ALAD deficiency was suspected based upon unusual patterns of porphyrins and porphyrin precursors.…”

Case Report of Hereditary Coproporphyria Accompanied by Nystagmus and Vestibular Dysfunction

“…Cutaneous porphyrias often involve edema, redness and blistering of the skin [2], especially with UV exposure. The neurocutaneous porphyrias [3], VP and HCP, were candidates for additional diagnosis because they captured the remaining elements of the patient's ailment, namely, vestibular dysfunction. Such autonomic neuropathies are common with neurological forms of porphyria [2,4,5].…”

“…Porphyria research in the 1980s and 1990s largely pointed to enzymatic analysis for diagnostic confirmation of porphyria [2,5,11]. Recent literature suggests that porphyria diagnoses in a clinical setting should be confirmed via genetic study [3,4,12,13]. A gene panel was completed via array comparative genomic hybridization (aCGH) with specific detection for ALAS2, CPOX, FECH, HMBS, PPOX and UROD, the results of which were negative for deletion and duplication.…”