Heme, like chlorophyll, is a primordial molecule and one of the basic pigments of life. Disorders in the normal heme synthesis can cause human diseases, including certain anemias and porphyrias. The porphyrias are a group of eight rare diseases caused by inherited defects, each resulting from a defect in a different enzymatic step of the heme biosynthesis. These disorders are multisystemic, with variable symptoms, and represent a major burden for patients and families because of the unusual course of the disease, with disabling chronic symptoms scattered with life-threatening acute attacks. Acute porphyrias are often misdiagnosed because of their multiform clinical manifestations, which may mimic other (and more common) diseases. This under-recognized disease also reflects a lack of medical and disease awareness, as well as a lack of biochemical guidelines and laboratory methods for diagnosis. As clinical features alone are not specific enough to confirm the diagnosis of acute porphyria or to distinguish between the different forms of acute porphyria, knowledge and correct interpretation of the appropriate tests are essential for accurate diagnosis and subsequent management of the disease. Delayed diagnosis and inappropriate treatment of acute porphyrias can be fatal.

In Portugal, porphyrias are underdiagnosed. In 2017, the National Health Institute Dr Ricardo Jorge (INSA) started to implement the biochemical diagnosis of porphyrias, and since 2023 almost complete biochemical and molecular characterization of porphyrias has been available. INSA is now a reference laboratory for biochemical and molecular characterization of porphyria but it took a lot of hard work to convince the medical community that porphyrias existed and that it was ‘easy’ to make a porphyria diagnosis, mostly a biochemical one if the right specimens were collected. So, with some porphyria awareness campaigns, medical meetings, workshops, and leaflets, the medical community was awakened to these interesting diseases.

In 2023, a multidisciplinary panel elaborated a consensus paper to consolidate this awareness of Porphyria, aiming to provide guidance for an efficient and timely diagnosis of acute porphyrias and evidence-based recommendations for treatment and monitoring patients and their families in Portugal. (‘Portuguese Consensus on Acute Porphyrias: Diagnosis, Treatment, Monitoring and Patient Referral- Acta Med Port 2023 Nov;36(11):753–764’).

So, briefly, in 2022, of the 24 samples for porphyria request, we characterized 4 patients with porphyria. In 2023, of the 69 requests for porphyria, we characterized 12 patients with porphyria from the biochemical and molecular point of view. Last year, the National Authority of Medicines and Health Products, I.P. (INFARMED) approved the ribonucleic acid interference (RNAi) therapy (givosiran; GIVLAARI®, Alnylam Pharmaceuticals, Cambridge, MA, USA).

Porphyria exists, we just have to look for it!