Porphyria: What is it and what are its characteristics?

It is a group of disorders caused by anomalies in the chemical steps that lead to the production of heme.

Heme is a vital molecule for all organs of the body, although it is more abundant in the blood, bone marrow and liver.

Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).

Porphyrias are rare disorders that mainly affect the skin or nervous system and can cause abdominal pain. These disorders are often inherited, which means they are caused by abnormalities in the genes passed down from parents to children.

When a person has Porphyria, the cells do not change the chemicals in the body called porphyrins and porphyrin precursors in heme, the substance that gives the blood its red color. The body makes heme mainly in the bone marrow and the liver.

The bone marrow is the soft, spongy tissue inside the bones; It causes stem cells to become one of three types of blood cells: red blood cells, white blood cells and platelets.

The process of making heme is called the heme biosynthetic pathway. One of eight enzymes controls every step of the process. The body has a problem doing heme if any of the enzymes is at a low level, also called a deficiency.

Porphyrins and heme porphyrin precursors accumulate in the body and cause disease.

Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, mainly affect the skin.

Areas of the skin exposed to the sun become brittle and blistered, which can lead to infection, scarring, changes in skin color (pigmentation), and increased hair growth.

Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and cutaneous porphyria tarda.

Other types of porphyria, called acute porphyrias, mainly affect the nervous system. These disorders are described as “acute” because their signs and symptoms appear quickly and usually last a short time.

Episodes of acute porphyria can cause abdominal pain, vomiting, constipation and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations.

These signs and symptoms can be deadly, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and porphyria due to deficiency.

Two other forms of porphyria, hereditary coproporphyria and variegated porphyria, can present acute and cutaneous symptoms.

Porphyrias can also be divided into erythropoietic and hepatic types, depending on where the harmful compounds called porphyrins and porphyrin precursors first accumulate in the body.

In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria.

The health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly).

The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate mainly in the liver, leading to abnormal liver function and an increased risk of developing liver cancer.

Environmental factors can strongly influence the appearance and severity of the signs and symptoms of porphyria.

Alcohol, smoking, certain medications, hormones, other diseases, stress, and diets or periods without food (fasting) can trigger the signs and symptoms of some forms of the disorder.

In addition, exposure to sunlight worsens skin damage in people with skin porphyrias.

What are the types of porphyria?

Each of the eight types of porphyria corresponds to low levels of a specific enzyme in the heme biosynthetic pathway. Experts usually classify porphyrias as acute or cutaneous depending on the symptoms a person experiences:

  • Acute porphyrias affect the nervous system. They happen quickly and last a short time.
  • Cutaneous porphyrias affect the skin.
  • Two types of acute porphyrias, hereditary coproporphyria and variegated porphyria, may also present cutaneous symptoms.

Experts also classify porphyrias as erythropoietic or hepatic:

  • In erythropoietic porphyrias, the body over produces porphyrins, mainly in the bone marrow.
  • In hepatic porphyrias, the body over produces porphyrins and porphyrin precursors, mainly in the liver.

How common is porphyria?

The exact rates of porphyria are unknown and vary throughout the world. For example, cutaneous porphyria tarda is more common in the United States, and variegated porphyria is more common in South America.

Frequency

The exact prevalence of porphyria is unknown, but probably ranges from 1 in 500 to 1 in 50,000 people worldwide. In general, cutaneous porphyria is the most common type of porphyria.

For some forms of porphyria, the prevalence is unknown because many people with a genetic mutation associated with the disease never experience signs or symptoms.

Acute intermittent porphyria is the most common form of acute porphyria in most countries. It can occur more frequently in northern European countries, such as Sweden and the United Kingdom.

Another form of the disorder, hereditary coproporphyria, has been reported mainly in Europe and North America.

Variegated porphyria is more common in the population of South Africa; About 3 out of every 1,000 people in this population have the genetic change that causes this form of the disorder.

What causes porphyria?

Most porphyrias are inherited disorders. Scientists have identified genes for the eight enzymes in the heme biosynthetic pathway.

Most porphyrias result from the inheritance of an abnormal gene, also called genetic mutation, from a father.

Some porphyrias, such as congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and erythropoietic protoporphyria, occur when a person inherits two abnormal genes, one from each of the parents.

The likelihood that a person will pass the abnormal gene or genes to the next generation depends on the type of porphyria.

Cutaneous porphyria tarda is usually an acquired disorder, which means that factors other than genes cause the deficiency of the enzyme. This type of porphyria can be triggered by:

  • Too much iron
  • Use of alcohol or estrogen.
  • Chronic hepatitis C – a long-lasting liver disease that causes inflammation, or swelling of the liver.
  • HIV-the virus that causes AIDS.
  • Abnormal genes associated with hemochromatosis-the most common form of iron overload disease, which causes the body to absorb too much iron.

For all types of porphyria, the symptoms may be:

  • Consumption of alcohol.
  • Smoke
  • Use of certain medications or hormones.
  • Exposure to sunlight.
  • Stress.
  • Diet and fasting.