The acute hepatic porphyrias: Current status and future challenges

The porphyrias are predominantly inherited metabolic disorders which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis Historically they have been classified Into hepatic and erythropoietic forms based on the primary site of expression of the prevailing dysfunctional enzyme From a clinical point of view however It is more convenient to subdivide them into acute and non-acute porphyria thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks Unrecognised or untreated such an acute porphyric attack is associated with a significant mortality of up to 10% The acute hepatic porphyrias comprise acute intermittent porphyria variegate porphyria hereditary coproporphyria and delta-aminolevulinic acid dehydratase deficiency porphyria Making a precise diagnosis may be difficult because the different types of porphyrias may show overlapping clinical and biochemical characteristics To date the therapeutic possibilities are limited and mainly symptomatic In this overview we report on what is currently known about pathogenesis clinic diagnostics and therapy of the acute hepatic porphyrias We further point out actual and future challenges in the management of these diseases