PhD defence L.G. (Louisa) Kluijver

Below is a brief summary of the dissertation:

Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disorder that causes painful skin reactions after exposure to (sun)light. The disease results from an enzyme defect in heme synthesis, leading to the accumulation of the toxic substance protoporphyrin IX (PPIX). PPIX is activated by light, causing phototoxic reactions. Additionally, PPIX accumulates in the liver and bile ducts, which can lead to serious complications such as gallstones, liver cirrhosis, and life-threatening liver crises. Since 2016, treatment with afamelanotide has been available, which reduces the number of phototoxic reactions, but this treatment is not accessible to all patients.
This thesis explores the systemic consequences of EPP. Vitamin D deficiency is common, even in patients treated with afamelanotide. Adequate vitamin D supplementation is essential to prevent and treat vitamin D deficiency and related porous bones, which is prevalent in this population. Life-threatening liver crises and their treatment with exchange transfusions are discussed; these are more effective than plasmapheresis in reducing toxic PPIX levels. Due to high mortality and the risk of recurrent crises, early bone marrow transplantation, the only curative treatment, is recommended.
Children with EPP experience a significantly lower quality of life compared to healthy peers and adults with EPP, highlighting the urgent need for effective treatments. Furthermore, a relationship was found between hormones and PPIX levels: testosterone increases PPIX, while estrogen may decrease it. Finally, a warning is issued against phototherapy in newborns with EPP due to the risk of severe skin reactions.