Porphyrias

This is a group of rare disease causes by various errors of porphyrin biosynthesis, genetic or acquired.

– Porphyrin is made in a series of enzyme reactions.

– Depending on the faulty part, there is accumulation of either porphyrinogens (unstable precursors of porphyrins) or initial reactants like d-aminovulinic acid.

– The initial reactants are neurotoxic, whilst porphyrins induce photosensitivity + free radical formation.

Acute intermittent porphyria

This is an autosomal dominant condition due to a defect in porphobilinogen deaminase, which is much more common in females

– The results in the toxic accumulation of d-aminolaevulinic acid and porphobilinogen

– It characteristically presents with acute intermittent attacks from triggers, often in young women.

Triggers:

– Infection

– Surgery

– Drugs

– Cytochrome P450 enzyme inducers

Symptoms:

GI –> abdominal pain, vomiting (colic and fever)

Neuro –> Seizures and motor problems

Cardio –> Sympathetic overload gives hypertension + tachycardia

Psychiatric –> Mood disturbances (depression and anxiety)

If urine is left to stand it will turn deep red

Diagnosis:

– Urine shows raised porphobilinogen levels

– RBC enzyme essay –> shows deficiency in the enzyme porphobilinogen deaminase

– Blood test shows raised serum levels of d-aminolaevulinic acid and porphobilinogen

Management:

– 1st line is IV Haematin (inhibits production of porphyrinogen precursors)

– IV fluids (correct electrolytes) + high carbohydrate diet

Porphyria Cutanea Tarda

This is a liver-based porphyria which is due to a problem with uroporphyrinogen decarboxylase

– This is a more chronic porphyria and does not present as acute intermittent attacks

Causes:

– Genetic defect in enzyme or due to liver damage (alcohol, hepatitis C)

Symptoms:

– Photosensitive rash on the face and hands with skin fragility and blisters.

– Excess hair growth all over body with darkening of the skin

Tests:

– Urine shows ­raised levels of uroporphyrinogen

– Pink fluorescence of urine under UV light using a Wood’s lamp.

Management:

– Phlebotomy (guided by serum iron levels)

– Chloroquine can be used