Porphyrias are a group of rare inherited disorders. An important part of hemoglobin, called heme, is not made properly. Heme is also found in myoglobin, a protein found in certain muscles. Normally, the body makes heme in a multi-step process and porphyrins are made during several steps of this process. People with porphyria are lacking certain enzymes needed for this process. This causes abnormal amounts of porphyrins or related chemicals to build up in the body.
Porphyria is inherited through an autosomal dominant process (with the exception of Doss porphyria). This means one parent has to have the disorder for it to be passed down through the family and each child will have a 50% chance of inheriting this hyperactive enzyme.
Porphryias are complex disorders, with different prognosis (at times unpredictable), and have a great variety of symptoms and signs. Nonetheless it is important to note that the great majority of carriers of this genetic defect can be asymptomatic their whole life.
There are many different forms of porphyria. The most common type is porphyria cutanea tarda (PCT).
Porphyria Cutanea Tarda (PCT)
This disease is the most common of the porphyrias and results from a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD).
There are familiar and sporadic forms of the disorder, being the sporadic the most frequent (around 80% of the cases). In it, the enzyme hyperactivity stays on the liver tissue and may reach normal values once the disorder is in remission. There is not a familial affectation. The origin of sporadic porphyria is unknown but it is suggested that alcohol, iron overload and hepatic viruses inactivate the enzyme in those individuals with the defect.
Familial PCT is also an autosomal dominant disease.
A form of toxic or environmental PCT can also be triggered by halogenated aromatic hydrocarbons, some of which can cause porphyria in laboratory animals as well as in humans.
In Spain, PCT is the most frequent form of porphyria (1.24 cases of 1000 in Madrid).
The overproduction and accumulation of prophyrins is detected in the plasma, urine and liver. This build-up is the cause of the skin symptoms: blisters in uncovered areas of the skin, especially on the back of the hands. These form scabs that when they dry and fall off, leave a characteristic hyper- or hypo-pigmented scar. The skin is very fragile to even the smallest traumas and hypertrichosis (over- abundance of hair growth) can also occur. This skin type of porphyria generally appears in individuals over 40 years of age and does not differentiate between sexes, although there are cases of early onset in familial PCT, in toxic PCT and in cases triggered by oral contraconceptive medicines.
PCT hepatic lesions are more dependent on alcohol consumption or a hepatic viral infection than by porphyria itself which makes its prognosis variable. The evolution of the liver disease in PCT contributes to, among other things, siderosis. The iron deficiency inhibits the activity of the enzymatic system, origin of the disorder. Therefore, iron overload alters heme metabolism. The disease can go into remission in some forms and cases when the triggering factors are eliminated.
GENE OR REGION STUDIED