Erythrocyte Protoporphyrin Levels Research Articles

Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort.

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited. Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide. A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment (p < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment. This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.

When the diagnosis is written in the DNA: a case of erythropoietic protoporphyria in a patient with a chromosome-18 deletion.

In this case study, we describe a 21-year-old man with erythropoietic protoporphyria who sought medical attention in April 2022 for diffuse edema and erythema of the hands. These symptoms had been present since childhood and usually occurred soon after sun exposure. The patient's medical history showed that chromosome 18's long arm had partially deleted. We performed a number of tests, including measuring total erythrocyte protoporphyrin levels and utilizing a spectrofluorometer to assess the fluorometric emission peak of plasma porphyrins, based on the patient's medical history and clinical symptoms. Furthermore, a genetic analysis identified an intronic variant on one allele, c.315-48T>C (IVS3-48T>C), which is categorized as a susceptibility polymorphism, and a complete deletion of the ferrochelatase gene on the other allele. The patient's clinical condition improved following the June 2022 afamelanotide implant procedure.

Two Novel Mutations in FECH in a Patient With Erythropoietic Protoporphyria: A Case Report

Introduction: Erythropoietic protoporphyria (EPP) is a rare photodermatosis mainly caused by deficiency of the enzyme ferrochelatase (FECH). We herein report a case of EPP associated with 2 novel mutations in FECH. Case presentation: A 15-year-old boy experienced pain and pruritus after sunlight exposure. He had occasional claret-red urine, hepatomegaly with increased alanine aminotransferase and aspartate aminotransferase levels, and an elevated free erythrocyte protoporphyrin level. He was treated with oral β-carotene and cholestyramine and avoidance of sunlight as much as possible. Discussion: Genome sequencing revealed 2 novel FECH mutations that had been inherited from his healthy parents. Pathogenicity analysis involving prediction using PolyPhen-2, SIFT, and Mutation Taster revealed that the 2 novel mutations were likely pathogenic. Although the patient’s parents were healthy, they each had one of these 2 mutations. This finding is consistent with previous reports stating that individuals carrying low-expression alleles can be asymptomatic. The pathogenesis of the disease caused by these 2 mutations requires verification by larger and more detailed studies. Conclusion: Although the precise role of these mutations in EPP is not clear, the findings in the present case expand the genotypic spectrum of the disease.

A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria

The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18 years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30 ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325 mg twice daily was administered for 12 months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12 months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8 years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3 months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n = 8; median relative difference: -0.21 (IQR: −0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP.Trial registration: NCT02979249.

Recovery From Severe Systemic Peripheral Neuropathy Secondary to Erythropoietic Protoporphyria by Liver Transplant: A Case Report

Erythropoietic protoporphyria is a rare inherited metabolic disorder involving the heme biosynthesis pathway and leads to the accumulation of protoporphyrin in the erythrocytes or liver. Although peripheral neuropathy is known to develop occasionally in other types of porphyria, it rarely occurs in patients with erythropoietic protoporphyria. A 16-year-old boy was transferred to our hospital due to end-stage liver disease secondary to erythropoietic protoporphyria. Severe systemic peripheral neuropathy, similar to that presented in Guillain-Barré syndrome, developed; it was promptly managed with mechanical ventilation. Electrophysiological assessment of the presented neuropathy showed no responsiveness, indicating severe axonopathy. Six weeks after the transfer, liver transplant was performed.Postoperatively, hepatorenal syndromes improved immediately, and his erythrocyte protoporphyrin level decreased from 6291 to 174 μg/dL red blood cells.The patient started to move his limbs gradually and was weaned from mechanical ventilation 2 months after liver transplant. Eventually, he was discharged from hospital and was able to ambulate with assistance 10 months after liver transplant. To our knowledge, this is the first report detailing the clinical course in a patient with erythropoietic protoporphyria who recovered from severe systemic peripheral neuropathy after liver transplant.

Relationship between blood Lead status and anemia in Ugandan children with malaria infection

BackgroundIn Uganda, childhood anemia remains a health challenge and is associated with malaria infection as well as iron deficiency. Iron deficiency is intertwined with nutritional status, age and other comorbidities including helminths and Lead toxicity. Environmental Lead levels accounts for one’s blood Lead (BL) levels. Blood Lead competitively blocks iron absorption, inhibits hemoglobin (Hb) biosynthesis and elevates free erythrocyte protoporphyrin (FEP) levels. Lead toxicity’s contribution towards anemia pathogenesis, especially during malaria infection has not been studied. Concomitant exposure to both malaria infection and Lead pollution, exacerbates the anemia status. This study therefore aimed at expounding the anemia status of these Ugandan children aged under 5years who are exposed to both malaria infection and environmental Lead pollution.MethodsBriefly, venous blood samples from 198 children were microscopically assayed for malaria parasite density (PD), and hemoglobin (Hb) concentrations using the cyanmethemoglobin method, while BL and FEP levels were determined by the standard atomic absorption spectrophotometric and fluorometric methods respectively.ResultsOne hundred and fifty-one (76.3%) of the children analyzed had moderate anemia (Hb <10>5 g/dL) with Means of BLL=8.6 µg/dL, Hb =7.5 g/dL, FEP/Hb =8.3 µg/g and PD =3.21×103 parasites / µL, while eight (4%) were severely anemic (<5 g/dL). Regression analysis and statistical correlation between PD and Hb (r = -0.231, R2= 0.15 P-value < 0.001) was negative and weak as compared to that between FEP/Hb and Hb (r = -0.6, R2=0.572 P-value=0.001).Conclusion Based on the study’s findings, we conclude that BL significantly contributes to the pathogenesis of anemia and therefore its co-existence with malaria infection in the host exacerbates the anemia status.

Iron deficiency, still a rarity in children with sickle cell anemia in Ile-Ife, Nigeria

In this study, children with sickle cell anemia were evaluated for iron deficiency. Serum ferritin and free erythrocyte protoporphyrin free erythrocyte protoporphyrin (FEP) levels, mean corpuscular volume mean corpuscular volume (MCV) and mean corpuscular hemoglobin mean corpuscular hemoglobin (MCH) were used in determining their iron status. The study was done at Pediatric Hematology Outpatient Clinic of the Obafemi Awolowo University Teaching Hospitals’ Complex, Ile-Ife. Forty-eight HbSS subjects in steady state and 48 apparently well age and sex matched HbAA controls were evaluated. Serum ferritin less than 25ng/dL FEP greater than cut off for age, mean corpuscular volume MCV and mean corpuscular hemoglobin MCH less than cut off for age were regarded as indicating iron deficiency. Serum ferritin values ranged from 34.2 to 3282.9μg/L, with a mean of 381.2 (1.0), median 180μg/L; which was significantly higher than the controls (p=0.000). FEP was lower in the subjects but none was iron deficient compared with the controls. The mean corpuscular hemoglobin MCH of subjects was significantly lower than the controls. Subjects had lower mean corpuscular volume MCV compared with controls. Iron deficiency was not detected in any of the subjects with sickle cell anemia in comparison to a prevalence of 43.75% in the controls. Iron deficiency anemia (IDA) was found in 16.7% of the controls, using the WHO cut off for anemia which is hemoglobin concentration of <11g/dl. While a high prevalence of iron deficiency was noted in the control group, patients with sickle cell anemia were largely iron sufficient, despite their anemia. Iron supplementation remains unnecessary as part of routine management of children with sickle cell anemia in our practice.

Longitudinal Analysis of Erythrocyte and Plasma Protoporphyrin Levels in Patients with Protoporphyria

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited cutaneous porphyrias resulting from decreased activity of ferrochelatase and gain-of-function mutations of δ-aminolevulinic acid synthase-2, respectively. Both of these protoporphyrias cause increased protoporphyrin levels that cause photosensitivity and may lead to hepatopathy and further increases in erythrocyte and plasma porphyrin levels. We evaluated erythrocyte protoporphyrin and plasma porphyrin levels in all subjects with EPP (83 subjects) or XLP (9 subjects) without evidence of liver disease tested repeatedly at a single laboratory over 25 years. Intersubject variation contributed more than intrasubject variation (78.86% vs 21.14%) to overall variability, and longitudinal variability, estimated by CV, averaged 26%. Erythrocyte total protoporphyrin levels were similar in males and females with EPP (ratio, 0.99; 95% CI, 0.82-1.21; P = 0.96) but were higher in males than females with XLP, although this difference was not statistically significant (ratio, 0.76; 95% CI, 0.43-1.36; P = 0.35). Analysis of 20 subjects from 9 separate families showed significant effects of family compared with effects of individual variation on total variance (50% vs 25%; P < 0.0001). Variation of erythrocyte total protoporphyrin up to 25% is expected in patients with protoporphyria, whereas greater increases might raise concern for protoporphyric hepatopathy.

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

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.

The phototoxicity of vemurafenib: An investigation of clinical monochromator phototesting and in vitro phototoxicity testing

BackgroundVemurafenib is a targeted therapy approved for the treatment of patients with metastatic melanoma harbouring the BRAF V600E mutation. Photosensitivity has been reported in over 50% of patients and has been demonstrated to involve at least the broadband UVA spectrum in most patients. Erythrocyte protoporphyrin levels have also been reported as elevated in some patients. ObjectivesWe report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted. ResultsAfter one month of vemurafenib therapy the patient demonstrated markedly increased light sensitivity in the UVA spectrum between 335±27nm, 365±27nm and 400±27nm. However responses in the UVB (305±5nm) and blue light (430±27nm) regions were normal. There was no abnormal immediate erythemal response. Pre-vemurafenib baseline phototesting was normal, as was repeat testing two months later when the patient was taking high doses of systemic steroid. No abnormal porphyrins were detected and the antinuclear antibody test was normal. In parallel studies, HaCaT keratinocytes incubated with vemurafenib were killed by UVA but not by visible (blue) light and did not show evidence of detectable intracellular porphyrin in the presence of the drug. ConclusionThese data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria.

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromosomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP.

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.

Loss-of-Function Ferrochelatase and Gain-of-Function Erythroid-Specific 5-Aminolevulinate Synthase Mutations Causing Erythropoietic Protoporphyria and X-Linked Protoporphyria in North American Patients Reveal Novel Mutations and a High Prevalence of X-Linked Protoporphyria

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inborn errors of heme biosynthesis with the same phenotype but resulting from autosomal recessive loss-of-function mutations in the ferrochelatase (FECH) gene and gain-of-function mutations in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene, respectively. The EPP phenotype is characterized by acute, painful, cutaneous photosensitivity and elevated erythrocyte protoporphyrin levels. We report the FECH and ALAS2 mutations in 155 unrelated North American patients with the EPP phenotype. FECH sequencing and dosage analyses identified 140 patients with EPP: 134 with one loss-of-function allele and the common IVS3-48T>C low expression allele, three with two loss-of-function mutations and three with one loss-of-function mutation and two low expression alleles. There were 48 previously reported and 23 novel FECH mutations. The remaining 15 probands had ALAS2 gain-of-function mutations causing XLP: 13 with the previously reported deletion, c.1706_1709delAGTG, and two with novel mutations, c.1734delG and c.1642C>T(p.Q548X). Notably, XLP represented ~10% of EPP phenotype patients in North America, two to five times more than in Western Europe. XLP males had twofold higher erythrocyte protoporphyrin levels than EPP patients, predisposing to more severe photosensitivity and liver disease. Identification of XLP patients permits accurate diagnosis and counseling of at-risk relatives and asymptomatic heterozygotes.

Asymptomatic congenital lead poisoning – case report

Context. Congenital lead poisoning is uncommon and there is no consensus on the management of the newborn. Case Details. A female infant was born to a lead-burdened woman identified by screening just prior to delivery. Maternal blood lead level (BLL) was 58 μg/dL. The infant's BLL on the second day of life was 72 μg/dL with a free erythrocyte protoporphyrin level of 175 μg/dL. The child was managed by an exchange transfusion followed by chelation. The BLL 6 h after exchange transfusion was 11.4 μg/dL. Follow-up 2 years later showed a BLL of 9 μg/dL and normal development. Discussion. We present the details of a case of congenital lead poisoning treated aggressively which appears to have resulted in a favorable outcome.

Multiple contributors to iron deficiency and anemia in Senegal

Background Anemia, especially due to iron deficiency early in pregnancy, has adverse consequences on pregnancy outcomes.Methods A cross-sectional study of 480 pregnant women in their second trimester was conducted in Senegal's capital, Dakar. Eighty women were selected per health center. Parasitological, dietary, and genetic factors were assessed to ascertain their relationship to anemia status and etiology.Results Thirty-nine percent of the women were anemic; only 12–13% of the women had any parasite. Daily heme iron was reported in 35% of women, but intake amounts were low. Intakes of iron inhibitors were frequently consumed. Mean hemoglobin and serum ferritin levels were significantly higher and erythrocyte protoporphyrin levels were lower in women who consumed iron inhibitors less frequently.Conclusions Results of this study can improve the current antenatal program in Senegal and similar West African countries. Educating about dietary iron inhibitors and encouraging patient compliance can be significant contributors to reducing anemia in pregnancy.

A Pilot Study Investigating the Safety and Efficacy of Injectable Hemin (Panhematin®) in Patients with Low to Intermediate-1 Risk Myelodysplastic Syndrome.

Abstract 4859 Authors J. M. Shammo1, K. Shell1, D. Rhoades1, A. Rizman1, K. E. Anderson2, M. Holmay3, I. Miller1, S. Gregory1 Institutions 1Rush University Medical Center, Chicago, IL, 2University of Texas Medical Branch, Galveston, TX, 3Director CNS Medical Liaisons, Lundbeck, Inc. Background Injectable hemin (Panhematin) is an iron-containing metalloporphyrin that is approved for the treatment of acute intermittent porphyria. Preclinical data indicate that hemin administration has the potential to stimulate progenitor cell growth and gamma globin chain synthesis. Clinical trial data from Europe on the use of hemin in myelodysplastic syndrome (MDS) suggest it can result in hematologic improvements in a subset of patients (Volin 1988, Timonen 1992). Objective This was an investigator initiated study aimed at evaluating the safety and efficacy of Panhematin in patients with low or intermediate-1 risk MDS. Response assessments were done at week 8, as defined by the International Working Group. Secondary endpoints included the alterations of ferritin, porphyrin, and hemoglobin F levels from baseline with treatment Patients and Methods Between 6/2007 and 10/2008, 6 patients (median age 73.5, range 64-80, men = 5, women = 1) were treated. All patients had a diagnosis of low or intermediate-1 risk MDS (International Prognostic Scoring (IPSS) score of 0-1), were transfusion-dependent or had hemoglobin values of ' 10 g/dL, had ' 10% blasts in bone marrow and peripheral blood, had platelet counts &gt; 50,000/ microL and absolute neutrophil counts (ANC) &gt; 500/microL. Patients received daily doses of Panhematin® at 3 mg/kg IV on days 1 through 4 of week 1, and weekly on day 1 of weeks 2 through 8. Efficacy and safety assessments, including bone marrow biopsies, were performed on Week 8. Partial and complete responders in any of the three cell lines were allowed to continue treatment for as long as they benefit. Patients who did not demonstrate a response or those whose disease had progressed at Week 8 were withdrawn from the study. Results Five of 6 patients completed 8 weeks of treatment and were evaluable for response assessment. One patient withdrew his consent. One patient received an additional 4 weekly doses after achieving an erythroid response and was later retreated for an additional 16 weeks. All other patients had stable disease and four of them remained transfusion dependent. Only 1 (with RARS) out of 5 evaluable patients met criteria for hematologic response. His baseline hemoglobin (Hb) of 7.3g/dL increased to 8.5g/dL at week 8, and peaked at 8.7g/dL at week 9. His bone marrow biopsy at week 8 revealed a decrease in ringed sideroblasts from 73% to 51%. Once off treatment, this patient's Hb dropped back to a near baseline level of 7.0g/dL. Approximately a year later (after protocol amendment allowed for re-treatment), he was retreated and his Hb again increased to 8.2 g/dL at week 8, peaking at 8.8 g/dL. In two patients with RARS (the responder and another patient), it was noted that the erythrocyte protoporphyrin level was initially elevated and rose even higher at week 8. Similarly, erythrocyte porphobilinogen deaminase (PBGD) and uroporphyrinogen decarboxylase (UROD) activities increased with treatment, especially in the one patient who responded. In that patient, these activities decreased again after treatment ended. The reticulocyte count increased from 0.0294 to 0.0411 × 10 6/mcL only in this patient. There was no correlation observed between response to panhematin and HbF levels. Treatment was well tolerated in all patients and no major toxicities were observed. Conclusions In this small study of hemin treatment of patients with low to Int-1 risk MDS, one patient responded with increases in hemoglobin and in reticulocytes. The increases in reticulocytes and in erythrocyte PBGD and UROD in the responder may indicate an increase in erythropoeisis resulting in a larger proportion of young erythrocytes in peripheral circulation after treatment. Clearly, such observations need validation in larger studies, which may result in better understanding of MDS disease biology. Disclosures Shammo: ovation pharmaceutical: Research Funding. Off Label Use: the use of Panhematin in MDS.

Acquired erythropoietic protoporphyria

Dear Editor,Porphyrias are a group of diseases characterized byaberrations in the heme biosynthetic pathway. They canbe classified according to the primary site of the enzymaticdefect (i.e., hepatic versus erythropoietic) or according totheir clinical presentation into acute versus chronic ornoncutaneous versus cutaneous forms. Among the cutane-ous porphyrias, erythropoietic protoporphyria (EPP) standsout as the only form characterized by an immediate painfulreaction to sunlight [ 1].We report a case of an acquired variant of EPPdeveloping in a patient with myelodysplastic syndromemost likely due to the genetic instability associated with thedisease.A 66-year-old Caucasian man presented for the evalua-tion of stinging –burning pain that developed immediatelyafter exposure to sunlight and was restricted to the exposedskin. The condition had started 4 years earlier and hadbecome so severe that the patient avoided direct sunlightcompletely. Densely woven fabrics but not sunscreens orwindow glass provided protection. On physical examina-tion, we found mild, waxy thickening with small, scar-likedepressions of the skin over the nose and the backs of thehands. The patient had been evaluated earlier for poly-morphic light eruption, solar urticaria, and lupus erythema-tosus without positive results. The patient's history wasremarkable for a myelodysplastic syndrome (myelodys-plastic syndrome –refractory anemia with ringed sidero-blasts) that had been diagnosed 4 years earlier at about thesame time when the skin symptoms had appeared. Anemiawas the leading symptom of the myelodysplastic syndromeand was treated with repeated erythrocyte substitution.Examination of native blood and bone marrow smearsrevealed autofluorescence of a large proportion of thepatient's red blood cells (Fig. 1). Biochemical analysisshowed increased levels of free erythrocyte protoporphyrin(241 µg/dl red blood cells, normal range C, 252 A > G) in the ferrochelatasegene together with a so far undescribed polymorphism(IVS2 + 169 G > A) in intron 2 [ 2, 3]. Larger deletionswere excluded by fluorescence in situ hybridizationanalysis. A diagnosis of acquired EPP was made and

Vitamin D deficiency in patients with erythropoietic protoporphyria

The main symptom of patients with erythropoietic protoporphyria (EPP) is painful photosensitivity, starting within minutes of sun exposure and leading to sun-avoidance. As 80-100% of vitamin D is synthesized under the influence of sunlight, we investigated whether the avoidance of sunlight exposure in the Dutch EPP patient population causes vitamin D deficiency. Furthermore, we studied the relation between vitamin D levels, total erythrocyte protoporphyrin and quality of life. In a cross-sectional study of 48 Dutch EPP patients (mean age 41.4 years; range 16-77; 23 male, 25 female), we assessed serum 25-hydroxyvitamin D (25(OH)D) levels between June and November 2007, as well as total erythrocyte protoporphyrin (TEP) levels and Dermatology Life Quality Index (DLQI) scores. Mean serum 25(OH)D was 66 nmol/L (range 18-140, quartiles 36, 87). Twenty-two patients (46%; 15 male, 7 female) were vitamin D deficient. There was a significant difference (p = 0.029) in mean serum 25(OH)D between female (mean 75 nmol/L, range 18-140) and male patients (mean 55 nmol/L, range 18-115). The level of serum 25(OH)D showed a negative correlation with total erythrocyte protoporphyrin (TEP) (Pearson rank correlation (r(p)) = -0.337; p = 0.034). Serum 25(OH)D was inversely associated with scores of the Dermatology Life Quality Index (DLQI) (Spearman's rho correlation (r(s)) = -0.486; p = 0.001). The prevalence of vitamin D deficiency is high in the Dutch EPP population, especially in male patients, and correlates with the severity of EPP. Screening for and treatment of vitamin D deficiency should therefore be implemented in the care of these patients.

Bone marrow iron and plasma ferritin in dialysed patients given intravenous iron-dextran.

Bone marrow biopsies have been taken in 28 patients on or approaching maintenance haemodialysis before and after treatment with monthly intravenous iron-dextran (Imferon). Stainable marrow iron was compared with blood Hb, plasma ferritin, erythrocyte protoporphyrin and MCH levels at the time of biopsy, and with previous or subsequent responses to iron in terms of blood Hb and MCH. There was a positive correlation between bone marrow iron and plasma ferritin levels both before and after iron therapy. All the patients with excess marrow iron had high plasma ferritin. However, six patients with low or normal marrow iron also had high plasma ferritin, two of these before iron therapy was given. Seven of the eight patients with no detectable marrow iron had low plasma ferritin. Three of the 28 patients failed to respond to iron with an increased blood Hb. MCH increased in all patients studied during iron therapy. All but one of the patients with high plasma ferritin prior to iron therapy responded well to iron. Although a good correlation between plasma ferritin and marrow iron can be shown in dialysed patients given intravenous iron-dextran, a high plasma ferritin level in an individual patient should not by itself preclude iron therapy.