Disorder Of Heme Synthesis Research Articles

Surgical treatment for breast cancer in a patient with erythropoietic protoporphyria and photosensitivity: a case report

BackgroundErythropoietic protoporphyria (EPP) is a rare disorder of heme synthesis. Patients with EPP mainly show symptoms of photosensitivity, but approximately 20% of EPPs are associated with the liver-related complications. We report a case of breast cancer in a 48-year-old female patient with EPP in whom meticulous perioperative management was required in order to avoid complications resulting from this disease.Case presentationThe patient was diagnosed with EPP at the age of 33 and had a rich family history of the disease. For right breast cancer initially considered as TisN0M0 (Stage 0), the right mastectomy and sentinel lymph node biopsy were performed, while the final stage was pT1bN0M0, pStage I. In the perioperative period, we limited the drug use and monitored light wavelength measurements. Besides, we covered surgical lights, headlights, and laryngoscope’s light with a special polyimide film that filtered the wavelength of light causing dermal photosensitivity. After the surgery, any emerging complications were closely monitored.ConclusionsThe surgery, internal medicine, anesthesiology, and operation departments undertook all possible measures through close cooperation to ensure a safe surgery for the patient with a rare condition.

Mysterious disease porphyria: challenge of diagnosis. Analysis of the clinical case of porphyric polyneuropathy

Brief overview represents the description of the relationship between the clinical picture of porphyria and the description of vampires in the literature. Porphyria is a group of hereditary diseases caused by disorders of heme synthesis, with an increase in the level of its precursors in the blood and urine. The most characteristic description of vampires in the literature are the clinical manifestations of congenital erythropoietic porphyria. The most frequent and severe form of porphyria is an acute intermittent porphyria. The triad of seizures, acute abdominal pain and hyponatremia in young women are clear evidence of the disease. During an acute attack most patients can experience various psychiatric disorders. The dangerous complication of porphyria is the development of motor axonal or axonal‑demyelinating polyneuropathy. A definite marker of acute porphyria attacks is the urine excretion of various shades of red color. The actual mechanisms of damage to nervous system tissue are poorly understood, focal lesion of the brain in porphyria is not specific. Laboratory confirmation of porphyria is elevated urinary excretion of aminolevulinic acid, porphobilinogen, uroporphyrin and coproporphyrin. In the article the clinical presentation of a patient with porphyric polyneuropathy is described with the following one‑year dynamic observation. Management of acute attack with intravenous heme, increased glucose supplementation in the acute period of the disease, followed by physical rehabilitation of the patient in the recovery period, will help restore lost functions. However, the main idea is to explain to a patient what drugs are porphyrinogenic and necessity to change his life style.

Doss Porphyria (δ-Aminolevulinic Acid Dehydratase Porphyria) Presenting with Acute Onset Flaccid Paralysis

δ–Aminolevulinic acid dehydratase porphyria is an autosomal recessive disorder of heme synthesis resulting from deficiency of δ-aminolevulinic acid dehydratase (ALAD). Patients present with fatal neurovisceral manifestations and motor neuropathy. Here we report a patient with rapidly progressive flaccid tetraplegia with respiratory and bulbar paralysis. The importance of early diagnosis, prompt treatment and screening of relatives is stressed.J Nepal Paediatr Soc 2015;35(3):280-282

Liver Transplantation for Erythropoietic Protoporphyria With Hepatic Failure: A Case Report

Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excessive production and biliary excretion of protoporphyrin. The main clinical features—photosensitivity and hepatobiliary disease that may progress to liver failure—are caused by the toxicity of protoporphyrin. Orthotopic liver transplantation is an effective treatment of liver failure caused by EPP. In this report we have described an EPP Chinese man with end-stage liver disease. He was successfully transplanted. A 3-year follow-up study of protoporphyrin levels, liver tests, and liver biopsies showed no EPP recurrence after liver transplantation.

Sequential Liver and Bone Marrow Transplantation for Treatment of Erythropoietic Protoporphyria

Erythropoietic protoporphyria is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excess production and biliary excretion of protoporphyrin. The main clinical features, photosensitivity and hepatobiliary disease that may progress to liver failure, are caused by the toxicity of protoporphyrin. Liver transplantation has been used to treat liver failure in erythropoietic protoporphyria, but excess production of protoporphyrin by the bone marrow continues causing recurrence of liver disease in the majority of patients. This is the first report of successful sequential liver and bone marrow transplantation in a patient with liver failure as a result of erythropoietic protoporphyria. This combination corrected the severe phenotype, resolving the severe photosensitivity and halting erythropoietic protoporphyria associated liver graft injury. Splenectomy seemed to facilitate the successful bone marrow transplant.

Aortic valve replacement in a patient with erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis that causes excessive accumulation of protoporphyrin. The predominant clinical feature is photosensitivity triggered by light at wavelengths near 400 nm. We describe a 52-year-old man with EPP who underwent aortic valve replacement due to severe regurgitation. To prevent burn injuries, astral lamps in the operating room were covered with yellow film filters. Preoperative autologous blood donation was not undertaken. Blood priming of the extracorporeal circuit was performed to maintain adequate hemoglobin concentrations, which resulted in reduction of heme synthesis. The patient was discharged in good health without any signs or symptoms of EPP.

Novel Effects of Heme Biological Systemst and Heme-related Compounds in Biological Systems

Abstract: Heme and heme-related compounds such as porphyrins have a variety of biological and clinical activities. This review highlights some of the novel effects of these compounds in medicinal chemistry. Heme which has no photoreactive properties, can serve as the prosthetic group for various hemoproteins, or as a substrate for microsomal heme oxygenase (HO). In contrast, porphyrins have photodynamic activities but usually do not serve as substrates in biological systems. Thus, heme and heme analogues are often used to influence enzyme activities in tissues, while porphyrins by taking advantage of their photoreactive properties are used as drugs in medicine. There are four major applications of these compounds, namely the use of (i) heme in the treatment of porphyrias and hematological disorders, (ii) synthetic metalloporphyrins in the treatment of hyperbilirubinemia, (iii) metal-free porphyrins in photodynamic therapy of malignant tumors, and (iv) porphyrin derivatives as contrast reagents in radiography. Solubility, stability, pharmacokinetics, pharmacodynamics and analytical techniques are all important considerations in the medicinal chemistry of these compounds. In man and animals in vivo, the rate of synthesis and catabolism of heme, as well as disorders of heme synthesis are important in understanding pathophysiological effects of these compounds.

Porphyria Cutanea Tarda in a Patient With Agnogenic Myeloid Metaplasia

Porphyria cutanea tarda (PCT) is a syndrome characterized by skin lesions occurring predominantly in areas exposed to sunlight. Skin changes include increased fragility to mechanical trauma, subepidermal vesicles or bullae, erosions, hyperpigmentation and hypopigmentation, hypertrichosis, sclerodermoid changes with associated scarring alopecia when the scalp or other hair-bearing areas are involved, dystrophic calcification, and milia.¹The syndrome is caused by a disorder of heme synthesis in which uroporphyrinogen decarboxylase (URO-D) is deficient. Two forms of PCT have been described.²The first is inherited as an autosomal-dominant trait, and the URO-D deficiency is evident in both hepatocytes and RBCs.^2,3The second type of PCT is called the sporadic form, and the URO-D deficiency is demonstrable only in hepatocytes.⁴Both forms vary in their onset of symptoms; patients usually do not become symptomatic until after the fourth decade of life.¹Disorders associated with PCT to varying degrees include

Free Erythrocyte Protoporphyrin (FEP) II. The FEP Test is Clinically Useful in Classifying Microcytic RBC Disorders in Adults

Microcytic red blood cells (RBC) are commonly encountered in clinical medicine and are caused by disorders of heme synthesis [usually iron deficiency anemia (IDA) or anemia of chronic disease (ACD)] or disorders of globin synthesis (usually thalassemia syndromes or HbE). Using the clinical history and standard laboratory tests (hematocrit, per cent saturation of transferrin (% sat), serum ferritin, Hb electrophoresis, HBA2, and HbF) we classified 198 adults with microcytic RBC as follows: 48 IDA, 11 probable IDA, 11 iron-deficient erythropoiesis without anemia, 13 ACD, 42 alpha-thalassemia trait, 35 probable alpha-thalassemia trait, 20 beta-thalassemia trait, and 15 unclassified. In addition, we demonstrated that the FEP test reliably (83-90% of the time, depending on FEP methodology) classifies microcytic RBC states into disorders of heme synthesis vs. disorders of globin synthesis. Because of reliability and ease of measurement, we recommend the hematofluorometer FEP as the first step in the clinical laboratory evaluation of microcytic RBC disorders in both adults and children.

Porphyria cutanea tarda and pregnancy

Porphyria cutanea tarda (PCT) is an inborn error of metabolism. It is one of a family of six genetically distinct porphyrias and is characterized by a disorder of heme synthesis, resulting in the excess accumulation and excretion of uroporphyrins and coproporphyrins. To the best of our knowledge this is the first report of a successful pregnancy in a patient undergoing active therapy for this biochemical and clinical abnormality.

Uroporphyrin I stimulation of collagen biosynthesis in human skin fibroblasts. A unique dark effect of porphyrin.

Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [(3)H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5- to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities). No changes in morphology of the treated cells occurred. These studies indicate that porphyrins possess previously undemonstrated biological effects that are independent of their photosensitizing properties. This novel dark effect of uroporphyrin I may account for the sclerodermatous lesions seen in the skin of patients with porphyria cutanea tarda and erythropoietic porphyria.

THREE GENERATIONS OF HEREDITARY COPROPORPHYRIA (HC)

Hepatic porphyrias, disorders of heme synthesis, are rarely diagnosed in childhood. Two of three sons, ages 15 and 17 years, of a woman with longstanding neuromuscular disabilities eventually recognized to be associated with high urinary and fecal coproporphyrin (copro-P) exhibited similar biochemical findings. One son, DT, shows the typical porphyrin excretion pattern, whereas WT has only coproporphyrinuria. The mother took oral contraceptives over 10 years. How hormonal, nutritional and pharmacological factors contribute to the onset and clinical severity of the enzymatic defects in the porphyrias is not known. HC is rarely recorded (∼ 30 reported cases); to our knowledge the youngest was 10 years old. Thus, the incidence of latent carriers at risk is unknown.

Refractory Normoblastic Anemia with Sideroblasts in the Bone Marrow. A Disorder of Heme Synthesis

Refractory Normoblastic Anemia with Sideroblasts in the Bone Marrow. A Disorder of Heme Synthesis