Saturday, 12 January 2019

Porphyrias

Disease class: Metabolic diseases

Types

  • porphyria, Erythropoietic
  • porphyrias, Hepatic

The porphyrias are a group of rare metabolic disorders, characterised by dysfunctional biosynthesis of haem, the core protein of haemoglobin

 

Etymology

The name porphyria comes from the Greek πορφύρα (porphúra) meaning purple. This is because urine may turn red-purple during a porphyria attack, due to accumulation of these precursor substrates.

 

Pathophysiology

Haem production is the result of a long path of metabolic processes. Each step in the path is catalysed by an enzyme. The rate of conversion from substrate to product is determined by the enzyme activity. This means the rate of substrate removal is determined by enzyme activity. Here is a (very) simplified pathway:
Porphyrin precursors >1> porphyrins >2> haem


Each porphyria gene produces an enzyme with insufficient activity. This means that the substrate for that particular enzyme accumulates, since it is being produced faster than it is being removed. 

If step 1 is faulty, there will be too many porphyrin precursors since their rate of conversion is too low. These accumulate in the body and they induce photosensitivity and toxic radical formation. 

If step 2 is faulty, there will be normal levels of precursors, but too many porphyrins. These accumulate in the body and cause neurovisceral symptoms.

 

Acute porphyrias

In these three diseases, there is an accumulation of the neurotoxic porphyrin precursors. They are autosomal dominant.
The following two diseases feature photosensitive blistering skin lesions and/or acute neurovisceral crises.
  • Variegate porphyria 
  • Hereditary coproporphyria 

 

Non-acute porphyrias  

In these diseases, there is an accumulation of porphyrins but not porphyrin precursors. They feature cutaneous photosensitivity and associated skin manifestations. There are no neurovisceral symptoms.
  • Porphyria cutanea tarda 
  • Erythropoietic protoporphyria 
  • Congenital erythropoietic porphyria 

 

Acquired disturbances of porphyrin metabolism

  • Alcohol
  • Iron deficiency
  • Lead poisoning

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