A boy experienced episodes of photosensitivity with rash and swelling on sun exposed sites from 6-months old. A diagnosis of EPP was made when he was 2-years old following monochromator photo-testing showing marked 7-hour sensitivity at 400±27nm [half maximum band width] nm and 430 ± 27 nm and biochemical testing showing positive porphyrin plasma scan, raised free blood protoporphyrin (99% metal-free) and highly elevated total erythrocyte porphyrins (146.7μmol/L, normal <1.7). Unusually in EPP, he also showed mildly increased urine porphyrins.

Genotyping showed homozygosity for 2 different variants in the ferrochelatase gene. The patient is homozygous for the likely pathogenic variant FECH c.502C>T, p.(Pro168Ser) and homozygous for the low expression variant c.315–48T>C. Having both mutations and such high levels of porphyrins present a high risk of phototoxicity and likely also present a high risk of serious liver disease. A younger sister, initially biochemically diagnosed on cord blood, has the same mutations alongside comparable porphyrin biochemistry. Their parents and two siblings are heterozygous carriers of both variants.

His mother reported a history of her mother’s cousin (her second cousin, once removed) dying of liver disease aged 9, and EPP is on his death certificate. Another ‘cousin’ died at age 3 years old, probably of the same disease.

Liver transplant has been used to treat EPP severe liver disease but is not curative as recurrence of liver disease occurs when the bone marrow continues to produce excess protoporphyrin. Additionally, liver function can deteriorate acutely making patients poor candidates for transplant. For this reason, Haematopoietic Stem Cell Transplant (HSCT) may be recommended in patients who have undergone a liver transplant or for those considered to be at higher risk of liver failure, to remove the primary source of the excess protoporphyrin.

After multi-national discussion this boy had an unrelated donor HSCT in early 2024 after intensive conditioning. He had mild liver veno-occlusive disease post-transplant but is doing well now. Total erythrocyte porphyrin levels have gradually reduced with time following his transplant and are now well within the normal range. The proportion of metal-free protoporphyrin has also decreased to normal levels and, following an initial increase post-transplant, his total urine porphyrins have now also decreased to normal levels. There has also been marked improvement in repeat photo-testing and he has been able to gradually reduce precautions against painful cutaneous phototoxicity, such as wearing gloves all the time. His younger sister, who carries the same severe variant of EPP and is therefore also at risk of severe protoporphyria liver disease, is now being ‘worked up’ for HSCT. To our knowledge, this is the first case of HSCT in EPP in Scotland.

The input from colleagues throughout IPNET is gratefully acknowledged in the management of this case