Congenital erythropoietic porphyria: a single-observer clinical study of 29 cases

Abstract

Summary Background Congenital erythropoietic porphyria (CEP) is an autosomal recessive cutaneous porphyria caused by decreased activity of uroporphyrinogen III synthase (UROS). Its predominant characteristics include bullous cutaneous photosensitivity to visible light from early infancy, progressive photomutilation and chronic haemolytic anaemia. Due to its rarity and genetic heterogeneity, clinical phenotypes are unclear and its impact on health‐related quality of life (HRQoL) has not been previously assessed. Objectives To define comprehensively CEP phenotypes and assess their impact on HRQoL, and to correlate these factors with laboratory parameters. Methods A single observer assessed patients with CEP from four European countries. Results Twenty‐seven unrelated patients with CEP, aged between 7·6 and 65 years, participated in the study. The patients came from the U.K. (17), France (4), Switzerland (4) and Germany (2). Additional data were obtained for two deceased patients. Newly characterized features of CEP include acute‐onset cutaneous and noncutaneous symptoms immediately following sunlight exposure, and pink erythematous facial papules. There was a lack of consistent genotype–phenotype correlation in CEP. The main poor prognostic factors in CEP are the early age of disease onset and haematological complications. Conclusions CEP is a multisystem disease; cutaneous, ocular, oral and skeletal manifestations also contribute to disease severity and impact on HRQoL, in addition to the haematological complications. The rarity of the disease can lead to delayed diagnosis. The lack of consistent genotype–phenotype correlation in CEP suggests a contribution to phenotype from other factors, such as environment, patients’ photoprotective behaviour and genes other than UROS. There is currently an unmet need for multidisciplinary management of patients with CEP.

Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis

“…Age of onset and severity of CEP are both highly variable. 98 In a retrospective study of 29 CEP patients, 66% suffered from chronic hemolytic anemia with variable severity. 98 Iron parameters are not described in these patients.…”

The Cutaneous Porphyrias

“…The Skin in CEP (Katugampola et al 2012a ) Severe photosensitivity begins in infancy with blisters developing in exposed skin on minimal light exposure. Phototherapy for neonatal jaundice may trigger lesions.…”

Cellular and Gene Therapy for Erythropoietic Porphyrias

“…As of 2012, 22 cases of HSCT for CEP have been described in the literature ( Table 2). [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] Age at transplantion was between 10 months to 14 years. Conditioning was essentially performed with busulfan and cyclophosphamide.…”