Porphyria: Enzyme Defect with Consequences

Porphyria is a group of rare metabolic disorders with multiple manifestations. Porphyria can be acute or chronic, cause minor or life-threatening symptoms, and affect a wide variety of organs. The diagnosis is therefore often not easy to make. Learn more about the causes, symptoms, diagnosis, and treatment of porphyria here.

How does porphyria develop?

As different as the forms are, they have one thing in common: the formation of porphyrins is always disturbed. Porphyrins are chemical compounds, usually with metals. They are responsible for the color of proteins, such as the green chlorophyll in plants and the red color of blood cells and muscles. Porphyrins are an important component in the organism of humans and animals, where they are broken down in the liver via intermediate stages and then give the bile its greenish color. Various enzymes are involved in this incorporation, conversion and degradation, especially in the bone marrow and liver. If one or more of them are not present or do not function properly, this process is disturbed. Such an enzyme defect may be inherited or acquired (for example, after lead poisoning).

What are the different forms?

There is not only one classification, but several, which are made according to different criteria. Thus, a distinction is made according to origin (congenital – acquired), site of enzyme formation (bone marrowliver), and mode of progression (acute – chronic). Depending on where the affected enzymes are predominantly formed, the

  • Erythropoietic form (disorder in the hematopoietic bone marrow) and
  • Hepatic form (disorder in the liver cells), and
  • A combination of these two (erythrohepatic form) distinguished.

For example, if the incorporation into blood cells or muscle protein is disturbed, the concentration of porphyrins and their precursors in the blood increases; the expert then speaks of porphyrinemia. If the conversion is disturbed, these tend to be deposited in the skin and other tissues and damage them. The concentration in the urine (porphyrinuria) or stool may also be elevated.

How does the disease manifest?

The symptoms depend on which enzyme is affected. In practice, the classification into forms with sudden onset (porphyria acuta) and with chronic course (porphyria chronica) has proven useful, as they are accompanied by typical symptoms. Acute forms are characterized by abdominal pain, cardiovascular complaints, neurological disorders and psychological abnormalities such as depression. Characteristics of chronic porphyrias, on the other hand, are changes in the skin when exposed to light.

Two important forms at a glance

By far the most common is the

  • Porphyria cutanea tarda (PCT), a chronic form that is likely to be inherited or acquired. A typical characteristic is the formation of blisters on light-exposed skin, for example, the back of the hand or neck. There is increased pigmentation and hair growth. In most cases, damage to the liver also occurs. The excreted urine darkens pink or brown under the influence of light.
  • Porphyria acuta intermittens (AIP) is a hereditary, life-threatening form. It usually first manifests in early adulthood. Certain factors such as infections and medications, as well as stress, alcohol, and hunger, can trigger an acute attack. The symptoms are varied. They range from abdominal colic with nausea and vomiting to fever, cardiac arrhythmias, and increased blood pressure to psychological and neurological changes such as paralysis, sensory disturbances, seizures, and impaired consciousness. Even respiratory paralysis can occur. Therefore, the affected person must be cared for in an intensive care unit during an acute attack. Also in this form, the urine darkens.

How is the diagnosis made?

Decisive are first medical history and the complaint with the mixture of symptoms. The final diagnosis and differentiation of the form is made by determining porphyrins and their precursors in the blood, urine and stool. Genetic testing may also be performed.

What therapy is available?

In all forms, the most important thing is to avoid the triggers. In PCT, photoprotective ointments can be applied as a supportive measure. By taking the antimalarial drug chloroquine, an attempt can be made to dissolve the porphyrins from the tissues. However, this treatment is limited in time. Bloodletting is also used.In AIP, the symptoms are treated with intensive care in the acute attack. The course depends on the form and whether the triggers can be avoided. A cure is not yet possible for any porphyria.