Diagnosis Of Erythropoietic Protoporphyria Research Articles

Erythropoietic protoporphyria: case reports for clinical and therapeutic hints

BackgroundErythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity. Herein we report our case series describing the successful use of cimetidine and analyzing potential phenotype-genotype correlations.Case presentationThis case series describes five patients presented to our Rheumatology Service complaining sun sensitivity. Blood exams and genetic analysis were consistent with the diagnosis of erythropoietic protoporphyria. Four of 5 patients received cimetidine in addition to standard therapies and the effect of treatment was evaluated by Erythropoietic Protoporphyria - Quality of Life questionnaire.ConclusionsErythropoietic protoporphyria usually manifests in early childhood after a short sun exposure. Skin manifestations are the main reason for investigations, although sometimes they can be more subtle, leading to a significant diagnostic delay. Skin diseases in children can have profound effects on their family and social relationships. A treatment with cimetidine appears to be an excellent therapeutic option in children with Erythropoietic protoporphyria.

Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases

Erythropoietic protoporphyria (EPP) is a rare inherited disease whose morbidity is about 1:75,000 to 1:200,000. It is caused by the deficiency of porphyrin ferrochelatase (FECH). Liver involvement in EPP is even rarer. The diagnosis of EPP with liver involvement mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing, which is still a huge challenge for both clinicians and pathologists. Here, 5 cases of EPP with liver injury were collected, and the clinicopathological features of these patients were analyzed. The clinical manifestations and laboratory examinations varied from person to person, whereas the liver biopsies showed that there were dark brown deposits within the hepatocytes, Kupffer cells, bile canaliculi and the lumen of bile ducts, which was a constant finding by histopathological examination. Gene tests were conducted in two of the five cases, and the results confirmed the diagnosis. Fully understanding of the diseases can help us reduce the rate of missed diagnosis and provide proper treatment as early as possible.

A Case of Erythropoietic Protoporphyria

A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Serum, plasma, and erythrocyte protoporphyrin levels were elevated, the findings of which are consistent with a diagnosis of erythropoietic protoporphyria. This paper discusses the diagnosis and etiology of the porphyrias.

Leukocytoclastic vasculitis masking chronic vascular changes in previously undiagnosed erythropoietic protoporphyria

A 31-year old man presented with swelling and purpura of the dorsum of the hands following sun exposure. There was a preceding lifelong history of photosensitivity, but this episode, which occurred after the recent commencement of oral iron therapy, and after recent alcohol ingestion, was much more severe than any preceding episode. Skin biopsy performed 48 h after the onset of symptoms showed features consistent with the early stages of leukocytoclastic vasculitis. Direct immunofluorescence showed homogeneous thick staining of the vessel walls with IgG, IgM and IgA, together with abundant perivascular fibrinogen. A subsequent periodic acid-Schiff (PAS) stain on the skin biopsy revealed thickening of the walls of dermal vessels, which was not discernible in routinely stained (hematoxylin/eosin) sections. The diagnosis of erythropoietic protoporphyria (EPP) was confirmed by significantly elevated erythrocyte protoporphyrin levels and positive plasma fluorimetry. The diagnosis of porphyria may have been missed by routine skin microscopy if not for the additional information provided by clinical history, direct immunofluorescence and PAS stain. The pathogenesis and histopathology of acute and chronic vascular changes in EPP are reviewed.

Erythropoietic Protoporphyria: Spectrum of Three Cases

Erythropoietic protoporphyria is a rare photodermatosis of childhood, and the diagnosis can be delayed. A deficient ferrochelatase enzyme leads to accumulation of protoporphyrins in the dermis, causing phototoxic burning. To report three cases with great variability in severity of symptoms and age at diagnosis. We discuss clinical and biochemical findings, mutation analysis, and therapeutic options. We report three cases with different degrees of photosensitivity, laboratory results, psychosocial impact, and preventive and therapeutic treatments. The diagnosis of erythropoietic protoporphyria was confirmed by both typical elevation of plasma porphyrins and the discovery of a mutated FECH gene. Erythropoietic protoporphyria should be suspected in any cases of childhood photosensitivity. Systemic complications are unusual. Mutation analysis confirms the diagnosis. Photoprotection is the cornerstone of treatment.

The prognostic value of cord blood analysis in erythropoietic protoporphyria: the ‘Duesseldorf Cord Blood Study’

Erythropoietic protoporphyria (EPP) is the most common porphyria in childhood, presenting with painful and burning skin sensations as well as erythema and edema after sun exposure. It represents an inherited disorder of heme metabolism that is due to a reduced ferrochelatase enzyme activity. The diagnosis is usually established when symptoms start by measuring elevated levels of protoporphyrin in erythrocytes. The aim of our study was to question the predictive value of cord blood analysis in newborn relatives of EPP patients as this may offer the earliest possible diagnosis of EPP in newborn relatives of affected patients. Erythrocyte porphyrin (EP) was measured immediately after birth in 18 newborn relatives of EPP patients. EP was correlated to the subsequent clinical follow-up of mean 9 years after birth. We found EP to be within reference values in all 18 newborn relatives of EPP patients at birth. Out of 14 patients who were included in the follow-up period of median 9 years, 13 remained asymptomatic whereas one boy developed the typical symptoms of EPP at the age of three in combination with elevated EP. Based on the findings of our study, we assume that cord blood analysis is not a reliable prognostic tool in EPP from the actual point of view.

Four Novel Mutations in the Ferrochelatase (FECH) Gene in Patients with Erythropoietic Protoporphyria (EPP).

Erythropoietic protoporphyria (EPP) is an autosomal dominant disease with incomplete penetrance, due to reduced activity of ferrochelatase (FECH), a mitochondrial enzyme that catalyzes the insertion of iron in the protoporphyrin molecule in the final step of the heme biosynthetic pathway. The disease is biochemically characterized by increased protoporphyrins in erythrocytes, plasma and faeces and normal levels in urine. The clinical manifestations have a childhood onset, characterized by mild to moderate cutaneous photosensitivity, mild anemia and, in 5–10% of the cases, by progressive hepatic failure. Diagnosis of EPP can be supported by the simple measurement with flow citometry of fluorescent erythrocytes in peripheral blood. The phenotype of EPP results from coinheritance of a mutated allele and a wild-type low expressed allele of the FECH gene that spans about 45 kb on the long arm of chromosome 18. The FECH gene encodes for a precursor of 423 amino acid residues that is targeted to the matrix side of the inner mitochondrial membrane via a 62 amino acid cleavable leader sequence. A single promoter directs both housekeeping and erythroid expression, but two polyadenylation sites produce two mRNAs of different length. The molecular analysis of FECH gene has allowed the identification of more than 100 different mutations responsible for EPP, showing a high genetic heterogeneity. Aim of this study was to search for molecular abnormalities in four patients with clinical and biochemical signs of EPP. Molecular analysis was performed by PCR and direct sequencing of the promoter, the entire coding region and the splicing junctions of the gene. In patients who remained negative for mutations, DNA analysis was completed by long-PCR and chromosome walking. In this study four different molecular defects have been identified: two missense mutations and two large deletions in the first region of gene. One A>G substitution at nucleotide 362 in exon 4 resulting in a Glu to Gly amino acid substitution at position 121; one change C>T in position 782 of exon 7 causing a Ser 261Phe substitution; the c.1-7887_67+2422del10376bp and the c.1-9628_67+2871del12566bp. Even though with different breakpoints, both deletions include a portion of upstream intergenic region, the promoter, the exon 1 and a portion of intron 1 of the FECH gene preventing the expression of the mutated allele. This deletions are probably caused by unequal intragenic recombination between ALU sequences which have been found close to the breakpoints. Recently others deletions involving ALU sequences were described suggesting that large deletions can affect the FECH gene and cause of EPP.

Erythropoietic Protoporphyria Masquerading as Angioedema in a 4-Year-Old Female

Angioedema is a common presentation with a broad differential, including rare disorders with which an allergist must be familiar. Our objective was to report a case of swelling of the hands and feet mimicking angioedema with hepatomegaly in a 4-year-old girl. The patient was evaluated for painful swelling of the hands and feet after exposure to sun. Examination revealed edema and erythema of the extremities and hepatomegaly. Laboratory evaluation included elevated liver transaminases and plasma protoporphyrin, with normal urine porphyrins. Liver biopsy confirmed the diagnosis of erythropoietic protoporphyria, a disorder of heme biosynthesis in which patients may present with photosensitivity and angioedema. It is important for allergists to recognize this entity in patients with cutaneous disorders of unclear etiology in order to prevent possible life-threatening sequelae.

Rapid molecular diagnosis of erythropoietic protoporphyria among Swiss patients.

Erythropoietic protoporphyria (EPP) is an autosomal dominant inherited disorder with incomplete penetrance. It is caused by partial deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. Measurement of protoporphyrin concentrations in red cells and feces, although sufficient for diagnosis of symptomatic EPP patients, fails to detect asymptomatic gene carriers. We have developed a molecular diagnostic procedure for rapid and reliable screening of five known mutations in the ferrochelatase gene among Swiss EPP patients in a single denaturing gradient gel electrophoresis (DGGE) gel.

Erythropoietic protoporphyria. The problem of a suitable screening test.

Erythropoietic protoporphyria (EPP) is characterized by increased red cell protoporphyrins and is included in the differential diagnosis of children presenting with photosensitivity. In the past 20 years, using the traditional solvent extraction qualitative screening test for blood porphyrins, the diagnosis of EPP had been missed in 9 out of 10 patients but recently, using fluorescence microscopy of erythrocytes, no patients with EPP have been missed. All 14 patients in Northern Ireland known to have EPP were recalled and it was found that fluorescence microscopic determination was positive in all cases. We recommend fluorescence microscopy as the screening test of choice for the detection of increased red cell porphyrins.

Rapid Quantitative Assay for Erythrocyte Porphyrins

The rapid quantitative microfluorometric assay for free erythrocyte porphyrins can be applied in the diagnosis of erythropoietic protoporphyria. The advantages of this assay are speed, accuracy, reproducibility, and lower cost, as compared with other biochemical methods now in use. When local facilities permit, this assay can be done on a wet blood specimen. Otherwise, drops of blood from the finger can be collected on filter paper that can be submitted by regular mail to a laboratory for quantitative analysis by this assay.

Rapid quantitative assay for erythrocyte porphyrins

The rapid quantitative microfluorometric assay for free erythrocyte porphyrins can be applied in the diagnosis of erythropoietic protoporphyria. The advantages of this assay are speed, accuracy, reproducibility, and lower cost, as compared with other biochemical methods now in use. When local facilities permit, this assay can be done on a wet blood specimen. Otherwise, drops of blood from the finger can be collected on filter paper that can be submitted by regular mail to a laboratory for quantitative analysis by this assay.