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1	Molekulární patologie vybraných porfyrií s kožní manifestací / Molecular pathology of selected porphyria with skin manifestation Sameh Anwar Hussein Farrag, Mohamed January 2015 (has links) Porphyria is a group of inherited metabolic disorders due to enzymatic defect of the heme biosynthesis resulting in the overproduction of the heme precursors' porphyrins in different body organs. The enzymes of the heme biosynthesis are encoded by corresponding genes in which any defect in any of these genes lead to a specific type of porphyria. Numerous mutations were detected in these genes leading to impairment in the enzyme function and therefore developing of the clinical manifestations of porphyria. The aim of the present work was to investigate the UROD gene in patients with porphyria cutanea tarda (PCT) and hepatoerythropoietic protoporphyria (HEP) as well as the FECH gene in patients with erythropoietic protoporphyria (EPP) on a molecular level. We identified numerous mutations in the FECH and the UROD genes in three different populations, Czech, Slovak, and Egyptian. We described the novel mutations in the UROD gene in HEP Arabic patients from Egypt as well in the FECH gene in patients with EPP of Czech and Slovak origin. We expressed mutatted UROD protein in prokaryotic system and found 19 % of the wild-type enzymatic activity. Moreover, the current study presents for the first time the frequency of the low expression allele IVS3-48c in the FECH gene in healthy controls from the Czech...
2	Molekulární patologie vybraných porfyrií s kožní manifestací / Molecular pathology of selected porphyria with skin manifestation Sameh Anwar Hussein Farrag, Mohamed January 2015 (has links) Porphyria is a group of inherited metabolic disorders due to enzymatic defect of the heme biosynthesis resulting in the overproduction of the heme precursors' porphyrins in different body organs. The enzymes of the heme biosynthesis are encoded by corresponding genes in which any defect in any of these genes lead to a specific type of porphyria. Numerous mutations were detected in these genes leading to impairment in the enzyme function and therefore developing of the clinical manifestations of porphyria. The aim of the present work was to investigate the UROD gene in patients with porphyria cutanea tarda (PCT) and hepatoerythropoietic protoporphyria (HEP) as well as the FECH gene in patients with erythropoietic protoporphyria (EPP) on a molecular level. We identified numerous mutations in the FECH and the UROD genes in three different populations, Czech, Slovak, and Egyptian. We described the novel mutations in the UROD gene in HEP Arabic patients from Egypt as well in the FECH gene in patients with EPP of Czech and Slovak origin. We expressed mutatted UROD protein in prokaryotic system and found 19 % of the wild-type enzymatic activity. Moreover, the current study presents for the first time the frequency of the low expression allele IVS3-48c in the FECH gene in healthy controls from the Czech...
3	Investigating the porphyrias through analysis of biochemical pathways. Ruegg, Evonne Teresa Nicole January 2014 (has links) ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms. Acute attack Acute intermittent porphyria Aminolevulinate Aminolevulinate dehydratase Aminolevulinate synthase B vitamins Biomodeling Cofactors Computational modeling Congenital erythopoietic porphyria Coproporphyrinogen oxidase Erythropoietic protoporphyria Ferrochelatase GABA Glucose therapy Glycine Heme Heme biosynthesis Heme deficiency Heme therapy Hepatoerythropoietic porphyria Hepatorenal Tyrosemia Hereditary coproporphyria Iron Iron deficiency anemia Kinetics Lead poisoning Liver transplant Micronutrients PLP Porphobilinogen Porphobilinogen deaminase Porphyria Porphyria cutanea tarda Porphyrins Prophylaxis Protoporphyrinogen oxidase Pyridoxal Pyridoxal phosphate Pyridoxine Serotonin Succinyl-CoA TCA cycle Tryptophan Tryptophan pyrrolase Uroporphyrinogen decarboxylase Uroporphyrinogen synthase Variegate porphyria Vitamin B6 Vitamin therapy Vitamins X-linked protoporphyria X-linked sideroblastic anemia

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