PORPHYRIA - WHAT DO WE WANT TO KNOW

·        Porphyria is a rare genetic condition that can be passed through families. The porphyrias are a group of disorders of the “haem biosynthesis pathway”.

·        Haemoglobin, which carries oxygen around the body in the blood, is made in the liver. Haemoglobin is formed as a result of a series of chemical reactions called the "haem biosynthesis pathway”. Each stage of the pathway is controlled by a specific enzyme. All porphyrias result from partial deficiency of one of the enzymes of the haem biosynthesis pathway.This can lead to a build-up of chemicals which cannot be processed efficiently by the defective enzyme. 

Porphyrias are a mainly inherited group of metabolic disorders which affect the haem biosynthesis pathway as a result of an enzyme defect. This can result in the accumulation or the excretion of porphyrins which are purple-red pigments of a crystalline nature.

The pathological classification is based on the stage of haem biosynthesis and the specific enzyme defect:

1. ALA dehydratase deficiency porphyria:enzyme ALA dehydratase

2. Acute intermittent porphyria: enzyme PBG dehydratase

3. Congenital erythropoietic porphyria: enzyme uroporphyrinogen cosynthase

4. Cutaneous hepatic porphria: enzyme uroporphyrinogen decarboxylase

5. Hereditary coprophyria: enzyme coproporphyinogen oxidase

6. Variegate porphyria: enzyme protoporphyrinogen oxidase

7. Erythropoietic protopophyria: enzyme ferrochelatase

·         A common factor in all types of porphyria is an increase in the rate limiting enzyme five aminolaevulinic (ALA) synthesis which initiates the haem biosynthesis.

Porphyria is commonly classified clinically into acute or non acute.

The acute porphyrias include:

• ALA dehydratase deficiency porhpyria

• Acute intermittent porphyria

• Variegate porphyria.

• Hereditary coproporphria

·         During acute episodes severe abdominal pain is often the most significant finding and can be mistaken for an acute abdominal condition. In addition, limb weakness,cardiovascular changes, neuropsychiatric,and photosensitive skin changes (with the exception of acute intermittent porphyria) are common.

·         Acute attacks can be precipitated by a wide range of common drugs and patients with porphyria carry such lists themselves.

·         However, many patients can have acute attacks without taking or having any drugs administered. It is thought these patients are more susceptible because of infections, alcohol, programmed or nonprogrammed weight loss, smoking, endogenous hormonal changes and being female of child bearing age (a four-fold increase).

·         If an acute attack is suspected expert medical help should be sought and arrangements made to transfer the patient to an appropriate facility immediately.Prevention of an attack is essential and it is important for healthcare professionals and patients to understand the following:

1. Safe drugs only should be used

2. Patients should be educated about precipitating factors

3. Alcohol and smoking should be restricted or discouraged

4. Patients should wear a medic-alert device

5. Dieting and weight loss should be avoided

6. Specialist advice regarding menstruation should be sought if it is thought this may precipitate an acute attack

7. Barrier creams should be used to prevent photosensitivity reactions

8. Pregnancy should be postponed until the disease is under control

·         During the administration of a drug it should remembered that any drug which increases the synthesis of cytochrome P450 enzymes in the liver will also increase the synthesis of haem. This can result in an acute attack. However, some drugs which does not induce P450 enzymes and haem synthesis may also precipitate porphyria so it is essential to always refer to a ‘safe drug’ reference text.

The non-acute porphyrias or cutaneous porphyrias.

·         Photosensitising porphyrins are deposited in the upper dermal layer which are responsible for the characteristic skin lesions. The types of non-acute (cutaneous) porphyria are:

• Congenital Erythropoietic Porphyria (Gunthers Disease)

• Erythropoietic Protoporphyria.

• Porphyria Cutanea Tarda (Cutaneous Hepatic Porphyria)-inherited or acquired.

Drugs to be used in these patients and type of Anaesthetic