Variegate porphyria is a type of porphyria that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the seventh step in haeme production. Haeme is a vital molecule for all of the body's organs. It is a component of haemoglobin, the molecule that carries oxygen in the blood.

Many people with this disorder never experience symptoms. When symptoms occur, they can include acute attacks (similar to acute intermittent porphyria), skin damage, or both. Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea, and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certain hormones, and stress.

Some people with variegate porphyria have skin that is overly sensitive to sunlight. Areas of skin exposed to the sun develop severe blistering, scarring, changes in pigmentation, and increased hair growth. Exposed skin becomes fragile and is easily damaged.

Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life. In addition to the health problems described above, children with this disorder may have mental retardation and grow more slowly than other children.

How common is variegate porphyria?

This type of porphyria is most common in the white population of South Africa; about 3 per 1,000 people in this population are diagnosed each year. The disorder occurs much less frequently in other parts of the world.

What genes are related to variegate porphyria?

Mutations in the PPOX gene cause variegate porphyria.

The PPOX gene makes an enzyme called protoporphyrinogen oxidase, which is critical to the chemical process that leads to haeme production. The activity of this enzyme is reduced by 50 percent in most people with variegate porphyria. In severe cases that begin early in life, the enzyme is almost completely inactive. Nongenetic factors such as certain drugs, stress, and others listed above can increase the demand for haeme and the enzymes required to make haeme. The combination of this increased demand and reduced activity of protoporphyrinogen oxidase disrupts haeme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack.

How do people inherit variegate porphyria?

Variegate porphyria is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to decrease enzyme activity and cause symptoms. More severe cases result from inheriting two copies of the altered gene.