Porphyria

Porphyrias are genetic diseases where there are defects in one of the enzymes required for porphyria synthesis. Porphyrins are circular molecules which consist of four porphobilinogen molecules. Many proteins contain porphyrins, including haemoglobin, myoglobin, cytochromes, and NO-activated guanylyl cyclase.

Porphyrias are rare disorders, but the prevalence varies significantly with geography. For example, in Scandinavia, the prevalence is higher. In the US the prevalence of all forms of porphyria is approximately 1:25 000, but in Norway it is approximately 1:5 000.

The most common porphyria worldwide is porphyria cutanea tarda, followed by acute intermittent porphyria and erythropoietic protoporphyria.

Diagnosis and evaluation

Elevated levels of porphyrins and porphyrin precursors in the blood is typical for porphyrias. Porphyrins may also be measured in urine and in faeces. Porphyrins make urine tea-coloured or purple, especially when exposed to sunlight, and these samples must be kept form light before analysis.

Genetic analysis may also be helpful in the diagnosis.

Porphyria cutanea tarda

Porphyria cutanea tarda (PCT) is the most common of the blistering cutaneous porphyrias. These forms of porphyria are characterised by chronic skin blistering, scarring, and pigment changes on skin exposed to sun. PCT is caused by abnormal uroporphyrinogen decarboxylase (UROD). It usually presents in adulthood, and 80% of cases are sporadic, the remaining familial. Many patients with PCT have iron overload.

PCT is the most treatable porphyria. Avoidance of sunlight, as well as reducing factors which exacerbate the disorder (like alcohol and smoking), is important. Treatment involves phlebotomy, which reduces the number of plasma porphyrins. Low-dose hydroxychloroquine may also be used.

Acute intermittent porphyria

Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias. These porphyrias cause acute and (despite the name) chronic symptoms. The most common symptom of acute hepatic porphyrias is abdominal pain, usually accompanied by neurological symptoms like insomnia, agitation, hallucination, seizure, and hyponatraemia. There may also be peripheral neuropathy, as well as other non-specific symptoms like vomiting and pain in any body part.

The diagnosis of acute porphyria is often delayed as these patients as people with acute abdomen usually undergo evaluation to rule out surgical disease, after which the evaluation stops, and because it's a rare disease with non-specific symptoms. However, a quick measurement of urinary (preferred) or blood porphobilinogen (PBG) is specific and sensitive.

Acute hepatic porphyria attack must be treated with haemin (a haeme supplement, which decreases porphyrin synthesis by negative feedback), which reduces complications and hastens remission.

Attacks may be precipitated by certain medications, hormonal changes, dehydration, or by starvation. Many medications are known to be possible triggers, and a list can be found here. Drugs which induce liver enzymes are usually unsafe, including oestrogen, valproate, spironolactone, trimethoprim-sulfamethoxazole, and many others.