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A Guide To Porphyria

Written by Barry A. Tobe, MD, Ph.D, FRCP(C)
Prepared for the Canadian Association for Porphyria

Disclaimer
Care has been taken to ensure that the information in this guide is accurate at the time of production. This information is, however, intended for general guidance only. The Canadian Association for Porphyria disclaims for itself and for the author of this guide, all responsibility for any mis-statements or for consequences of actions taken by any person while acting on information contained herein. Physicians and patients must make their own decisions about therapy according to the individual circumstances of each case.

Introduction
This guide is designed to serve as an introduction to the clinical condition called porphyria. The general concepts of this disease will be presented and then a more detailed description of each clinical entity will follow. The reader is recommended to discuss the disease with their doctor and to research the literature and internet further if more detailed information is desired.

What is Porphyria?
Porphyrins are a group of chemical compounds that occur in most living cells in both animals and plants. These organic compounds are combined with metals such as magnesium in the plant kingdom to produce chlorophyll and with iron in the animal kingdom to produce heme. They are involved in the control of the electron transport systems of the organism and are localized in the intracellular organelles called mitochondria. The mitochondria influence the production, accumulation and utilization of the energy needed for cell metabolism. The term porphyria refers to a group of diseases in animals, particularly humans that are caused by the overproduction and accumulation of groups of porphyrins and porphyrin precursors in specific and typical patterns. Each type of porphyria is associated with specific accumulations of porphyrin compounds and precursors to induce a relatively consistent constellation of symptoms, clinical findings and biochemical abnormalities. The metabolic defects that are associated with this group of diseases are localized primarily in the liver, the bone marrow and the red blood cells. They are associated with demonstrable abnormalities in individual enzyme activities and gene defects.

The porphyrin synthetic pathway begins with the combining of glycine and succinyl - coenzyme A to form delta-aminolevulinic acid (ALA). Two of these molecules condense to form a single pyrrole ring structure called porphobilinogen (PBG). Four of these small pyrrole rings become joined through a series of enzymatic reactions to ultimately form a large ring configuration or tetrapyrrole compound called protoporphyrinogen that, in turn, is the precursor of heme. This large ring structure has a specific spatial configuration that enables it to hold an activated iron molecule in the center of the ring in such a way that it can interact with reactive molecules such as oxygen. This type of iron - porphyrin complex, when attached to the protein called globin is called hemoglobin. It is this combination of the three segments, porphyrin, iron and globin that enables oxygen to be bound and transported preferentially by the red blood corpuscles since they contain large amounts of hemoglobin. The oxygen is picked up and bound to the hemoglobin as the blood passes through the lungs and then is released into the peripheral tissues by physico-chemical reactions. This particular ring type of configuration of the porphyrins gives them a red colour. Some porphyrins are colorless but will turn red when exposed to sunlight. A similar porphyrin structure in plants when combined with magnesium and a different protein forms chlorophyl which gives the plants their characteristic green colour.