Porphyria

I

Introduction

Porphyria, one of a series of rare, usually inherited disorders concerned with the formation of the vital biochemical substance haem. The conditions affect about 1 person in 50,000 in Britain, but are commoner in South Africa where the prevalence may be as high as 1 in 1,000 of the white population. This is thought to have arisen from a gene mutation in one or more individuals that was passed on to progeny.

II

How Haem Works

The porphyrin molecule is important in both animal and plant life. In plants it combines with magnesium to form chlorophyll, in animals, it combines with iron to form haem. Haem binds with various proteins to form a range of haemoproteins, of which the most important is haemoglobin, which is the protein and iron-containing compound that fills the red blood cells and transports oxygen from the lungs to the tissues of the body. The other haemoproteins include a number of essential liver enzymes based on the haem molecule. The formation of haem is a complex biochemical process involving, consecutively, a series of nine enzymes. The structure of the genes for eight of these has now been determined.

III

Causes and Diagnosis

The various porphyrias are due to deficiencies of individual enzymes in the process of haem production resulting from mutations in these genes. Because different enzymes may be affected, the porphyrias may take various forms—but in all types of the disease there is overproduction of haem precursor substances. A specific diagnosis of the type is made both clinically and by determining the proportion of these precursor protoporphyrins in the urine and stools. The urine is usually red, but it may be orange or brown, or may darken on exposure to light.

IV

Symptoms

The acute porphyrias are the most severe. They feature intermittent attacks of neurological, digestive system, and skin disorders, which may be precipitated by various drugs and other factors. Acute intermittent porphyria is the commonest and the most severe. Although inherited, the disease inexplicably becomes manifest in females five times as often as in males. Attacks are commonest among sufferers in their 30s. Often there is no known family history and it is thought that the condition sometimes remains latent or unidentified for generations. Nearly all attacks start with severe, diffuse abdominal pain that can often be controlled only by strong painkillers. There is nausea and vomiting. People with first attacks sometimes undergo unnecessary surgery.

Nerve malfunction with tingling progressing to paralysis occurs in some 50 per cent of attacks. In the most severe cases, respiratory paralysis, unless skilfully managed, may prove fatal. Psychiatric manifestations are also a common feature during attacks. These may involve severe agitation, or mania, or depression. Often they include hallucinations which may appear like schizophrenia. Sometimes these patients are misdiagnosed as suffering from a primary psychiatric disorder. The psychiatric complications may, however, persist between attacks.

A large number of prescription drugs may precipitate attacks in affected people, so it is essential that these drugs be avoided and alternatives to them prescribed. Alcohol, too, can precipitate an attack, as can hormonal changes (such as those brought on during the menstrual cycle, or by oral contraceptives) or severe dieting.

The non-acute porphyrias are, generally, less severe. Porphyria cutanea tarda features redness, itching, blistering and discoloration of the skin when exposed to sunlight. This form may, however, also involve severe liver disease and 25 per cent of patients develop diabetes. The most important causal factor of this type of porphyria is alcohol taken in excess. Because of the link with haem, patients with a form of porphyria commonly develop anaemia. There are many other, less common forms of the disease.