6- WHICH biochemistry

The porphyrias could be classified more accurately on the basis of specific enzyme deficiencies. Other types of classification are based on the main clinical features; they are useful from the clinical point of view, but can present overlapping.

The acute porphyrias cause the onset of neurological symptoms that usually have an intermittent pattern. Cutaneous porphyria cause photosensitivity of the skin.

Acute intermittent porphyria, porphyria by ALA dehydratase deficiency, hereditary porphyria coproporphyria and varied are the acute porphyria. Porphyria cutanea tarda, hereditary coproporphyria, porphyria variegata,  protoporphyria, erythropoietic porphyrias are cutaneous porphyria. Hepatic porphyria and in those erythropoietic, the excess precursors come mainly respectively by the liver and bone marrow.

The porphyrias are a family of diseases caused by deficiencies of enzymes involved in the production of heme. Heme is a chemical compound that contains iron and gives blood its red color. Heme is the key component of several important proteins in the body, such as hemoglobin, which enables red blood cells to carry oxygen. Heme is also an important part of certain enzymes produced by the liver.” (source Italian Merck’s Manual)

originale da The Lancet
original by The Lancet

“Heme is produced in the bone marrow and liver through a complex process regulated by eight different enzymes. These enzymes work one after the other in separate steps that take the starting compound through several different intermediate compounds (heme precursors, also called porphyrins), then produce heme. If there is a deficiency in one of these enzymes, certain heme precursors may accumulate. They can accumulate in bone marrow or liver, excess appear in the blood and are excreted in urine or faeces. The accumulated heme precursors cause symptoms.  The specific heme precursors that accumulate and symptoms that develop depend on which enzyme is deficient. ” (source Italian Merck’s Manual)

The heme synthesis requires 8 enzymes (see Table) to produce and to process the molecular species called porphyrins ( and their precursors ) ; the accumulation of these substances determines the clinical symptoms of porphyria .

originale da rarediseasesnetwork.epi.usf.edu
original by rarediseasesnetwork.epi.usf.edu

The ‘subject’ of the liver’s enzyme system is called the cytochrome P450 system. Numerous medications, nutrients, and herbal therapies are metabolized through the cytochrome P450 (CYP450) enzyme system, as they can inhibite or induce it, and once altered can be clinically significant. As example, CYP450 inducers and inhibitors are commonly ingested items such as grapefruit juice and tobacco, as alcool or garlic are specifically toxic.

“Most porphyrias is autosomal dominant. In terms of genetic prevalence , the two most common types are porphyria acute intermittent porphyria ( PAI ) and porphyria cutanea tarda ( PCT ) . The prevalence of each is about 1 / 10,000 , but the prevalence varies greatly between regions and ethnic groups.”  (source Merck ‘s Manual for Professionals)

This means that in a region or a city of 1,000,000 inhabitants , the probable number of carriers is about 100 people, if we talk about territories directly involved by Viking / Norman / Dutch spread. It is a luck if many of them appear to be asymptomatic or very low symptomatic, but it could be a blame if a part of those are treated for anything but not porphyria.

However , the phenomenon should not be underestimated and could be better developed.

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