04139 Acquired congenital erythropoietic porphyria secondary to treatment for haematological malignancy
Year: 2024
Type: conference-paper
Study design: Case Report
Abstract: Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease caused by a mutation of UROS gene in chromosome 10 leading to deficiency of cytosolic enzyme uroporphyrinogen III synthase which converts hydroxymethylbilane into uroporphyrinogen III. The reduced enzyme activity results in the disorder of haem biosynthesis in which hydroxymethylbilane spontaneously condenses into uroporphyrinogen I which accumulates in bones, erythrocytes, skin, and teeth (erythrodontia). Onset typically occurs at birth or early infancy. The porphyrin deposition in CEP is primarily characterised by severe cutaneous photosensitivity whereby exposure to ultraviolet light induces blistering and lesion formation leading to significant scarring and disfigurement of sun-exposed sites.A 76-year-old female presented with painful blisters, increased facial hair growth and dark urine 7–10 days following an erythropoietin infusion for 5q deletion myelodysplastic syndrome. Physical examination showed large fluid filled blisters on her hands, wrists, and lower arms and lesions on the scalp. No further erythropoietin infusions were given, and her symptoms resolved after 4 months. The patient had no history of similar blistering or lesions in the past and no erythrodontia.Plasma porphyrin scan showed a positive peak with maximum fluorescence at 618 nm. Urine porphyrin fractionation showed markedly elevated uroporphyrin of 1048.7 nmol/mmol (reference range 0 - 4.4) and coproporphyrin of 243.2 nmol/mmol (reference range 0 - 41.0) with a predominance of isomer I, and borderline raised 7-carboxyporphyrin of 35.4 nmol/mmol (reference range 0 - 2.2). Faecal analysis showed an increased total coproporphyrin of 124 nmol/g (reference range 0 – 46) with an elevated I:III isomer ratio. There was no significant increase in faecal 7-carboxylate porphyrin nor any evidence of isocoproporphyrins. Repeat urine porphyrin analysis 6 months later showed a similar pattern but with much lower levels of uroporphyrin (346.9 nmol/mmol) and coproporphyrin (70.4 nmol/mmol). The biochemical findings were consistent with CEP.Only a small number of late-onset CEP, secondary to an underlying haematological malignancy, have been reported. The onset of symptoms in this patient was triggered by erythropoietin infusion stimulating haem biosynthesis. The increased rate of haem formation overwhelms the deficient enzyme, triggering the accumulation of porphyrins, photosensitivity and cutaneous symptoms.
Authors: John Gilman, Amira Ibrahim, Saliha Haji, Liezel Griffin, Denise Darby
Institution: Northern Care Alliance NHS Foundation Trust
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402696223