The Porphyrias: Clinic, Diagnostics, Novel Investigative Tools and Evolving Molecular Therapeutic Strategies

Abstract

The porphyrias are clinically and genetically heterogeneous metabolic disorders resulting from a predominantly hereditary dysfunction of specific enzymes involved in heme biosynthesis. Today, the clinical, biochemical, and genetic characteristics of this fascinating group of diseases are well established. Recently, different in vitro and animal models have facilitated the investigation of etiopathologic mechanisms in the different types of porphyria and the development of causal treatment strategies such as pathway interference, enzyme replacement, and gene therapy. The continuous progress in basic science has made an invaluable contribution to the rapid translation of discoveries made in the laboratory into new diagnostics and therapeutics in the near future.

The Porphyrias

“…On the other hand, distinguishing between acute and non-acute porphyrias makes more practical sense in most medical disciplines and is thus used more commonly, since this also considers the potentially life-threatening acute neurovisceral attacks (Table 2) [1][2][3].…”

“…The group of cutaneous porphyrias includes porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP), hereditary coproporphyria, congenital erythropoietic porphyria, X-chromosomal dominant protoporphyria, and hepatoerythropoietic porphyria (Table 1) [1][2][3].…”

“…After diagnosis, patients should if possible be referred to a specialized porphyria center or to a physician who is well versed in this field. Interdisciplinary care can be recommended, especially as regards treatment [1][2][3].…”

Photosensitivity in the Elderly—Think of Late-Onset Protoporphyria

“…Erythropoietic protoporphyria is due to a defect in ferrochelatase. (Puy et al, 2010;van Serooskerken et al, 2010). Within the group of cutaneous porphyrias, skin symptoms can vary considerably with regard to acuity and age of onset.…”

“…Without racial or sex predilection, the disease has an estimated prevalence of 1 in 130,000 and is inherited in an autosomal semidominant manner (Puy et al, 2010;van Serooskerken et al, 2010).…”