Purpose of review: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies.
Recent findings: The development of clinical and biological porphyria networks improved the long-term follow up of cohorts. The ageing of patients have allowed for the identification of novel recurrently mutated genes, and highlighted long-term complications in acute hepatic porphyrias. The treatment of hepatic porphyrias by an RNAi-targeting hepatic ALAS1 is actually tested and may lead to improve the management of acute attacks.In erythropoietic porphyrias, the key role of ALAS2 as a gate keeper of the heme and subsequently hemoglobin synthesis has been demonstrated. Its implication as a modifier gene in over erythroid disorders has also been documented.
Summary: The knowledge of both the genetic abnormalities and the regulation of heme biosynthesis has increased over the last 5 years and open new avenues in the management of erythropoietic and acute hepatic porphyrias.