Treatment Options in Acute Porphyria, Treatment Options in Acute Porphyria, Porphyria Cutanea Tarda, Porphyria Cutanea Tarda, and Erythropoietic Protoporphyria and Erythropoietic Protoporphyria

Porphyrias are inherited metabolic diseases secondary to deficiencies in the activity of specific enzymes in the heme biosynthetic pathway. With the exception of the initial enzyme, catalytic deficiency at any of the seven subsequent steps in the heme biosynthetic chain may result in accumulation of toxic heme precursors [1].Clinically, the porphyrias are divided into two main groups: the acute porphyrias, which present with neuropsychiatric symptoms, and the cutaneous porphyrias, which are characterized by dermal photo-sensitivity. Two of the acute forms of porphyria also present with photosensitivity.The autosomal dominant porphyrias are acute intermittent porphyria (AIP), familial porphyria cutanea tarda (PCT), hereditary coproporphyria (HCP), variegate porphyria (VP), and erythropoietic protoporphyria (EPP). Two rare forms are inherited in a recessive fashion: 5-aminolevulinic acid dehydra-tase–deficient porphyria and congenital erythropoietic porphyria. Two mutations for PCT cause hepatoeryth-ropoietic porphyria.Most porphyrias have low clinical penetrance, and symptoms are often triggered by specific endogenous or environmental porphyrogenic factors. Residual enzyme activity usually is enough to satisfy the physiologic heme demands [2••]. However, the recessive condi-tions exhibit very low residual enzyme activity and high clinical penetrance, often with manifestations from early childhood [2••]. The same is true for the extremely rare homozygous or compound heterozygous conditions of AIP, HCP, and VP.Porphyria symptoms result from the action of neu-rotoxic or phototoxic metabolites produced in the liver or bone marrow. Liver transplantation [3,4,5••] and/or bone marrow transplantation (BMT) [6,7] may be the final therapeutic alternatives.