Porphyria

From Ganfyd

The porphyrias are a group of enzymatic disorders in the heme (haem) biosynthetic pathway resulting in a deficiency of haem and accumulation of haem precursors (porphyrins)

The disorder may be inherited or acquired.

Classified as hepatic or erythropoietic according to the site of accumulation of the porphyrins.

Acute intermittent porphyria

Acute intermittent porphyria (AIP) is the classic porphyria that is misdiagnosed until either finally considered in the differential diagnosis of recurrent abdominal pain or someone looks at the urine that has stood for a period in the acute attack. There is diversity in presentation. Mutations in the HMBS gene at 11q23.3 coding for hydroxymethylbilane synthase (porphobilinogen deaminase) cause deficiency at times of increases in the metabolic flux through the hepatic heme synthetic pathway through say stress, ingestion of dietary compounds or drugs can induce an acute attack. Induction of the rate-limiting enzyme, 5-aminolevulinate synthase (ALAS) results in the accumulation of toxic metabolites. Onset is usually after puberty. It may manifest with:

Consider if: Abdominal pain Hypertension Hyponatraemia

• Severe abdominal or other pain
  • Sometimes constipation and urinary retention
• Fluctuating neuro-psychiatric illness
  • Psychosis or severe agitation
  • Motor disturbances that can progress to respiratory paralysis
  • Depression
  • Paraesthesia
  • Seizures
  • Paralysis
• Tachycardia and hypertension
• Electrolyte disturbances
• The association with young adult chronic renal failure can be overlooked

While the cardinal sign of activation of the disorder is the voiding of red urine, catches are:

• May not occur
• It takes some time for oxygenation to take place and colour the urine
• The woods light examination of the urine that would confirm promptly usually requires a visit to the dermatology department
• Only some laboratories offer the service

Acute treatment

• IV glucose load (redirects metabolism)
• Heme or hemearginate

Prevention

Consider and intervene with classic precipitants (glucose rehydration or avoidance):

• Alcohol
• Infection
• Starvation
• Hormonal changes

For drugs that may cause an attack see Drug Database for Acute Porphyria

Porphyria cutanea tarda

• Caused by heterozygous mutation in the UROD gene at 6p21.3 coding for uroporphyrinogen decarboxylase
• Photosensitive dermatitis
• Uroporphyrin in urine
• Alcohol and oestogen aggravation
• Iron overload with cirrhosis late
• Similar in phenotype to the toxic photosensitive dermatitis caused by chlorinated hydrocarbons such as hexachlorobenzene

Hepatoerythropoietic porphyria

• Caused by homozygous mutation or multiple heterozygous mutation in the UROD gene at 6p21.3 coding for uroporphyrinogen decarboxylase
• Mutilating skin photosensitivity with usually onset in infancy

Variegata porphyria

• Caused by heterozygous mutations in PPOXgene at 1q22 that codes for protoporphyrinogen oxidase
• Can have acute presentations with abdominal pain and neuropsychiatric symptoms
• Photosensitivity
• Skin blistering and fragility
• Hyperpigmentation

Coproporphyria

• Caused by heterozygous mutations in POXgene at 3q12 that codes for coproporphyrinogen oxidase
• Acute attacks of neurologic dysfunction usually provoked by similar precipitants to acute intermittant porphyria
• Skin photosensitivity sometimes present

Acute hepatic porphyria

• Caused by mutations of the ALAD gene at 9q34 that codes for delta-aminolevulinate dehydratase (porphobilinogen synthase)
• The mutations have different phenotypes and can range from the asymptomatic to abdominal pain and polyneuropathy

Congenital erythropoietic porphyria

• Caused by mutations of the UROS gene at10q25.2-q26.3 that codes for uroporphyrinogen III synthase
• Photosensitivity with early onset mutilating deformity
• Hypertrichosis
• Red urine and even teeth can become stained red
• Haemolytic anaemia