Prenatal Diagnosis in Congenital Erythropoietic Porphyria by Metabolic Measurement and Dna Mutation Analysis

Ged, Cécile; Moreau‐Gaudry, François; Taine, Laurence; Hombrados, Isabelle; Calvas, Patrick; Colombiès, P; Verneuil, Hubert de

doi:10.1002/(sici)1097-0223(199601)16:1<83::aid-pd812>3.0.co;2-4

Cited by 34 publications

(11 citation statements)

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“…These murine findings closely resembled those in human patients with the C73R/ C73R or other severe, transfusion-dependent genotypes, who present with hydrops fetalis or a transfusion-dependent phenotype and a severe microcytic hypochromic anemia with marked reticulocytosis, abnormal erythrocyte morphology and medullary and/or extramedullary expansion (1,3,4). To date, nine C73R/C73R probands have been reported (6,(26)(27)(28)(29)(30)(31); porphyrin levels were provided for four patients. Of these, the mean urinary total URO and COPRO I and III isomers was 40 μmol/L, with a range of 14-78 μmol/L (6,28-30), compared to a mean of 100 μmol/L for the C73R/ C73R mice.…”

Section: Discussionmentioning

confidence: 99%

“…Human C73R/C73R newborns are already porphyrin loaded, since these infants have developed cutaneous lesions within 2 weeks of birth (29,30). Another C73R/ C73R CEP newborn, who had hyperbilirubinemia, was treated with phototherapy and developed severe blistering lesions due to the high porphyrin concentration present at birth (27). Some C73R/C73R infants may not survive (6) unless they are chronically transfused from birth (29,30), whereas others are candidates for bone marrow or hematopoietic stem cell transplants (26,28).…”

Section: Discussionmentioning

confidence: 99%

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Congenital Erythropoietic Porphyria: Characterization of Murine Models of the Severe Common (C73R/C73R) and Later-Onset Genotypes

Bishop

Clavero

Mohandas

et al. 2011

Mol Med

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Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder due to the deficient activity of uroporphyrinogen III synthase (UROS). Knock-in mouse models were generated for the common, hematologically severe human genotype, C73R/C73R, and milder genotypes (C73R/V99L and V99L/V99L). The specific activities of the UROS enzyme in the livers and erythrocytes of these mice averaged approximately 1.2%, 11% and 19% of normal, respectively. C73R/C73R mice that survived fetal life to weaning age (~12%) had a severe microcytic hypochromic anemia (hemoglobin 7.9 g/dL, mean cellular volume 26.6 fL, mean cellular hemoglobin content 27.4 g/dL, red cell distribution width 37.7%, reticulocytes 19%) and massively accumulated isomer I porphyrins (95, 183 and 44 μmol/L in erythrocytes, spleen and liver, respectively), but a nearly normal lifespan. In adult C73R/C73R mice, spleen and liver weights were 8.2-and 1.5-fold increased, respectively. C73R/V99L mice were mildly anemic (hemoglobin was 14.0 g/dL and mean cellular hemoglobin was 13.3), with minimally accumulated porphyrins (0.10, 5.54 and 0.58 μmol/L in erythrocytes, spleen and liver, respectively), whereas adult V99L/V99L mice were normal. Of note, even the mildest genotype, V99L/V99L, exhibited porphyria in utero, which disappeared by 2 months of age. These severe and mild mouse models inform therapeutic interventions and permit further investigation of the porphyrin-induced hematopathology, which leads to photoinduced cutaneous lesions. Of significance for therapeutic intervention, these mouse models suggest that only 11% of wild-type activity might be needed to reverse the pathology in CEP patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Congenital Erythropoietic Porphyria: Characterization of Murine Models of the Severe Common (C73R/C73R) and Later-Onset Genotypes

Bishop

Clavero

Mohandas

et al. 2011

Mol Med

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“…Twenty‐two different mutations of the uroporphyrinogen III cosynthase gene have been described to date. Prenatal diagnosis is now available, enabling diagnosis by amniocentesis at 16 weeks (31), thus families should receive genetic counseling. In CEP, molecular analysis has shown that most patients have different mutations on each allele and are thus compound heterozygotes (32); correlation of genotype and phenotype suggests a link between mutation type and disease severity (33).…”

Section: Geneticsmentioning

confidence: 99%

Diagnosis and management of the erythropoietic porphyrias

Murphy

2003

Dermatol Ther

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“…Twenty‐two different CEP mutations have been described to date. Prenatal diagnosis is now available, enabling diagnosis by amniocentesis at 16 weeks, 51 and thus, families should receive genetic counselling.…”

Section: Congenital Erythropoietic Porphyriamentioning

confidence: 99%

The cutaneous porphyrias: a review

Murphy

1999

Br J Dermatol

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Many patients with cutaneous porphyria have curable or controllable disease; untreated porphyria may prove fatal. The genetic defects and mechanisms underlying porphyria are steadily being delineated, treatments have become more appropriate and genetic counselling is now more accurate. A summary of the basic diagnostic features, management and recent advances in the cutaneous porphyrias is presented, based on a workshop held by the British Photodermatology Group.

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Prenatal Diagnosis in Congenital Erythropoietic Porphyria by Metabolic Measurement and Dna Mutation Analysis

Cited by 34 publications

References 11 publications

Congenital Erythropoietic Porphyria: Characterization of Murine Models of the Severe Common (C73R/C73R) and Later-Onset Genotypes

Congenital Erythropoietic Porphyria: Characterization of Murine Models of the Severe Common (C73R/C73R) and Later-Onset Genotypes

Diagnosis and management of the erythropoietic porphyrias

The cutaneous porphyrias: a review

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