Congenital erythropoietic porphyria (CEP) is an autosomal recessive metabolic disorder of which less than 300 cases are reported in the literature. It is caused by mutations in the UROS gene or rarely, mutations in the X-linked GATA1gene leading to deficiency of the enzyme uroporphyrinogen III synthase, the fourth enzyme in the heme biosynthesis pathway. This multi-system disorder is characterised by the build-up of uroporphyrin I and coproporphyrin I which causes extreme photosensitivity from birth. CEP can cause severe skin fragility including blisters and scarring, ophthalmologic complications including loss of vision, haemolytic anaemia, and dental and skeletal abnormalities. Disease severity is variable and dependent on the type of mutation, unknown genetic factors, environmental factors and photoprotective behaviour. CEP is normally managed by strict photoprotection and vitamin D supplementation. Blood infusions, splenectomy, stem cell and bone marrow transplantations, and gene therapy are also potential treatment options.

A 5-year-old patient presented to the dermatologist after his non-consanguineous parents noticed blisters and scarring on photo-exposed areas and darkly coloured urine during a holiday. On examination, he was found to have scarring and post inflammatory hyperpigmented patches on sun exposed areas, hypopigmentation on his nose and cheeks as well as slightly discoloured teeth. The patient is not known to have a family history of CEP.

Initial investigations included urinary, plasma and faecal porphyrin screens. Results showed raised urinary porphyrin:creatinine (2383 nmol/nmol, reference range <40) with markedly increased uroporphyrin I (96.3%) compared to uroporphyrin III (3.7%), as well as an increased coproporphyrin I (85.7%) compared to coproporphyrin III (14.3%) isomer ratio.

The plasma porphyrin screen showed a distinct immunofluorescence peak at 618 nm. His total faecal porphyrins were raised (310 nmol/g, reference <200) with a significantly increased coproporphyrin I (91.5%) to coproporphyrin III (8.5%) isomer ratio.

The pattern of results confirmed a biochemical diagnosis of CEP, however genetic analysis of known mutations was negative. The latter was performed using Nonacus enrichment technology (RCGPv5) and Illumina DNA sequencing to detect known pathogenic variants in the UROS and GATA1 genes.

In conclusion, this patient had a biochemical and clinical diagnosis of CEP, however negative genetic analysis demonstrates current genetic testing may not be able to detect all mutations causing CEP. RNA sequencing is planned to investigate gene expression in more detail.