What is Porphyrias

Porphyrias, Acute intermittent porphyria; Hereditary coproporphyria; Congenital erythropoietic porphyria; and Erythropoietic protoporphyria.

  • Blood – they are a group of disorders characterzed by photo-sensitivity, acute attacks of abdominal pain and neurologic abnormalities or both.
  • Porphyria Cutanea Tarda – disease with striking cutaneous manifestations.
  • Protoporphyria – inherited illness characterized by a unique type of photosensitivity.
  • Congenital Eyrthropoeitic Porphyria
  • Acute Intermittent Porphyria
  • Variegate Porphria and Hereditary Coproporphyria (VP and HCP)

 

Statistics on Porphyrias

  • Porphyria Cutanea Tarda – 1 in 25,000 caucasians, uncommon in African Americans.
  • Protoporphyria – this is relatively common but the exact incidence has not been determined. Hundreds of cases have been reported throughout the world.
  • Congenital Eyrthropoeitic Porphyria – Fewer than 300 cases have been rpeorted in the medical literature.
  • Acute Intermittent Porphyria – estimates of the defect have ranged from 1.5-10 per 100,000 but most carriers of a mutant allele never develop symptoms.
  • Variegate Porphria and Hereditary Coproporphyria – both are rare but VP occurs more often in South Africans of Dutch descent.

 

Risk Factors for Porphyrias

  • Porphyria Cutanea Tarda – this is a disease of adults, mainly middle aged men who use alcohol regularly. Due to an enzymatic defect that is inherited in about half of cases.
  • Protoporphyria – inherited mutation in the gene for an enzyme which is involved in the synthesis of heme.
  • Congenital Eyrthropoeitic Porphyria – due to a severe deficiency of uroporphyrnogen III co-synthase.
  • Acute Intermittent Porphyria – mutations in the gene encoding porphobilinogen deaminase are responsible. The result is a partial block in the heme biosynthetic pathway. It is transmitted as an autosomal dominant trait.
  • Variegate Porphria and Hereditary Coproporphyria – both disorders are due to the autosomal dominant transmission of mutant alleles resulting in enzymes that are deficient.

 

Progression of Porphyrias

  • PCT: If liver iron stores are depleted and liver toxins avoided then it is likely that PCT will not affect life expectancy. There have been some reports in Europe of an increased risk of hepatocellular carcinoma but this has not been confirmed elsewhere.
  • Protoporphyria – This is a benign disease in most patients and progresses very little. The complication of cirrhosis with liver failure is rare and the only effective therapy for this complication is liver transplantation.
  • Congenital Eyrthropoeitic Porphyria – bone marrow transplantation is the only therapeutic option that reverses the disease pehnotype but the procedure is feasible only when normal HLA matched sibling donors are available. If photomutilation can be avoided and if the haemolytic anaemia is not too severe, then affected individuals may lead long, productive lives.
  • Acute Intermittent Porphyria – If acute attacks are successfully prevented life expectancy is normal. Early effective treatment of the acute attcks that do occur usually prevents permanent nerve damage. The frequency of attacks in women usually declines after menopause.
  • Variegate Porphria and Hereditary Coproporphyria – the avoidance of offending drugs generally prevents the development of any attacks. If acute attacks are prevented, life expectancy is normal.

 

How is Porphyrias Diagnosed?

  • Liver Function Tests: transaminaseses may be raised in Porphyria Cutanea Tarda.
  • Full blood count: haemolytic anaemia common in Congenital Eyrthropoeitic Porphyria, leucocytosis is occasionally seen in attacks of Acute Intermittent Porphyria (VP and HCP).
  • Urea and Electrolites: hyponatraemia from SIADH is a common finding in Acute Intermittent Porphyria (VP and HCP).

 

Prognosis of Porphyrias

The porphyrias are life-long intermittent illnesses, but with good long-term management, the affected person can expect long problem-free periods.

 

How is Porphyrias Treated?

Porphyria Cutanea Tarda

  • Eliminate exposure to alcohol and oestrogen.
  • Removal of iron by repeated phlebotomy (500mL of blood every two weeks). Clinical remission often occurs after removal of about 3L of blood. If phlebotomy contraindicated then low doses of chloroquine phosphate can be given. Clinical remission usually after a few months and then treatment should be stopped (hepatic and haeamtologic side effects).
  • Reflective material such as zinc oxide may provide be useful until the effects of phlebotomy are achieved.

Protoporphyria

  • Topical sunscreens.
  • The induction of carotenaemia may result in increased tolerance to sunlight. This is done by adminstering beta-carotene beadlets. There is some technique to interrupt the enterohepatic circulation of protoporphyrin which has shown some promising results.
  • Cholecystectomy is indicated when gallstones are present.


Congenital Eyrthropoeitic Porphyria

  • Avoid exposure to sunlight.
  • Protective clothing and sunscreens.
  • Splenectomy and transfusions may be required.
  • Bone marrow transplantation may be useful in selected cases.

Acute Intermittent Porphyria and Variegate Porphria and Hereditary Coproporphyria

  • Harmful drugs should be withdrawn.
  • Morphine (and phenothiazines) may be used in treating pain and anxiety.
  • Careful monitoring of hydration.
  • Carbohydrates should be administered orrally or IV (as 10% dextrose) to achieve a 300-500g of daily glucose. If improvement not seen within a day intravenous hematin should be given. Clinical improvement should follow withing 24-48 hours.
  • Education concerning exposure to harmful drugs.
  • Sunscreens and appropriate clothing is the management of the cutaneous manifestations of VP and HCP.

 

Porphyrias References

  1. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001
  2. Cotran, Kumar, Collins 6th edition. Robbins Pathologic Basis of Disease. WB Saunders Company. 1999.
  3. Hurst JW (Editor-in-chief). Medicine for the practicing physician. 4th edition Appleton and Lange 1996.
  4. Kumar P, Clark M. CLINICAL MEDICINE. WB Saunders 2002 Pg 427-430.
  5. Longmore M, Wilkinson I, Torok E. OXFORD HANDBOOK OF CLINICAL MEDICINE. Oxford Universtiy Press. 2001