Congenital Erythropoietic Porphyria with Persistent Severe Biochemical Abnormalities and a Non-Mutilating Clinical Course: A Case Report
Afamelanotide may help manage photosensitivity in some CEP patients, but more research is needed to confirm its efficacy.
Where it sits
this study against the rest of the afamelanotide corpusSummary and findings
This case report describes a 32-year-old woman with congenital erythropoietic porphyria (CEP) who showed persistently elevated erythrocyte porphyrin levels but a non-mutilating clinical course. Genetic testing revealed a low penetrance intronic UROS variant. The patient experienced improvement in photosensitivity and pain after starting afamelanotide.
Abstract
Congenital erythropoietic porphyria (CEP), also known as Günther disease, is a rare autosomal recessive porphyria caused by deficiency of uroporphyrinogen III synthase, leading to accumulation of phototoxic type I porphyrins. CEP classically presents in infancy with severe photosensitivity, blistering, scarring, and hemolytic anemia; however, significant phenotypic variability has increasingly been recognized. We report 32-year-old women diagnosed with CEP in early infancy who demonstrated persistently and profoundly elevated erythrocyte porphyrin levels over more than a decade yet followed a relatively non-mutilating clinical course. Genetic testing identified a low penetrance intronic UROS variant typically associated with erythropoietic protoporphyria, underscoring diagnostic challenges and genotype-phenotype discordance. The patient experienced marked improvement in photosensitivity and burning pain after initiation of afamelanotide, without need for transfusion therapy or stem cell transplantation. This case highlights the heterogeneity of CEP, the importance of long-term biochemical follow up, and the potential role of afamelanotide in improving quality of life for selected patients with CEP.
Background
Congenital erythropoietic porphyria (CEP) is a rare genetic disorder characterized by severe photosensitivity and hemolytic anemia due to a deficiency in uroporphyrinogen III synthase. The condition typically presents in infancy and can lead to significant skin damage and other complications. This study explores a case of CEP with atypical presentation and examines the role of afamelanotide in managing symptoms.
Methods
The study is a case report of a 32-year-old woman with CEP, diagnosed in early infancy. Genetic testing was conducted to identify the UROS variant. The patient's clinical course and response to afamelanotide were documented over more than a decade.
Results
The patient maintained elevated erythrocyte porphyrin levels but did not experience the typical mutilating course of CEP. Genetic testing revealed a low penetrance intronic UROS variant. After initiating afamelanotide, the patient reported significant improvement in photosensitivity and burning pain, without requiring transfusion therapy or stem cell transplantation.
Interpretation
This case highlights the phenotypic variability in CEP and suggests that afamelanotide may improve quality of life for some patients. However, as a single case report, these findings are not generalizable. The genetic findings underscore the complexity of genotype-phenotype correlations in porphyria.
Key findings
- 32-year-old woman with CEP diagnosed in infancy.
- Persistently elevated erythrocyte porphyrin levels over more than a decade.
- Low penetrance intronic UROS variant identified.
- Marked improvement in photosensitivity and pain with afamelanotide.
Limitations
- Single case report
- Genotype-phenotype discordance
- No control group
- Long-term effects not assessed