Digenic inheritance of mutations in the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes in a unique type of porphyria.

The simultaneous dysfunction of two enzymes within the heme biosynthetic pathway in a single patient is rare. Not more than 15 cases have been reported. A woman with a transient episode of severe photosensitivity showed a biochemical porphyrin profile suggestive of hereditary coproporphyria (HCP), whereas some of her relatives had a profile that was suggestive of variegate porphyria (VP).

Novel null-allele mutations and genotype-phenotype correlation in Argentinean patients with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism in which decreased activity of ferrochelatase (FECH) leads to accumulation of protoporphyrin IX (PP IX) in red blood cells, plasma, liver, and bile, and increased PP IX excretion in feces. Clinically, EPP is characterized by photosensitivity that begins in early childhood and includes burning, swelling, itching, and painful erythema in sun-exposed areas. Chronic liver disease is an important complication in a minority of EPP patients, and in some cases liver transplantation has been performed.

Aminolaevulinic acid-induced protoporphyrin IX pharmacokinetics in central and peripheral arteries of the rat.

Photodynamic therapy (PDT) based on the photosensitive protoporphyrin IX (PpIX) may prevent restenosis after transluminal angioplasty. PpIX is synthesized in mitochondria, which differ in number and activity among various tissues. Therefore, we questioned whether the course of PpIX concentration after systemic aminolaevulinic acid (ALA) administration differed among various arteries.

Two course illuminating scheme improves aminolevulinic acid photodynamic therapy in cell cultures.

Photodynamic therapy with the pro-drug 5-aminolaevulinic acid (ALA-PDT) is being used for the treatment of Barrett's oesophagus. We postulated that a first early course of ALA-PDT would increase protoporphyrin IX (PPIX) accumulation and thus the efficacy of a second course of ALA-PDT, by manipulating ferrochelatase (FC) and porphobilinogen deaminase (PBG-d) activity. Human EBV-transformed lymphoblastoid cells were used as a model of human tumour cells for the ability to form haem is present in all cells.

Comparison of normal piglet bladder damage after PDT with oral or intravesical administration of ALA.

5-Aminolaevulinic-acid (ALA) can be used as an alternative drug in photodynamic therapy of the bladder, since the selective formation of protoporphyrin IX (PpIX) in the tumour and the virtual absence of induced skin photosensitivity are theoretically advantageous for clinical use. A preclinical study was performed, using an in vivo normal piglet bladder model, in order to determine the maximum drug and light doses for reversible tissue damage. Various ALA doses were administered either orally or instilled in the bladder and different radiant exposures were applied.