Porphyria

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Porphyria

• Congenital Erythropoietic Porphyria
• Steph Jacques, Jenna McIntyre, Alana Petersen
  Alicia Wood
• PHM 226

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Recall from last week..

• Basic building block of heme pyrrole ring
• 4 pyrrole rings Protoporphyrin IX
• Protoporphyrin IX Fe ? Heme
• Heme- prosthetic group that binds oxygen
• Heme found in hemoglobin, myoglobin and
  cytochromes

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What is porphyria?

• The porphyrias are a group of disorders caused
  by enzyme defects in heme biosynthesis leading to
  overproduction of porphyrins and their
  precursors1
• Porphyrias are classified as
• Erythropoietic
• Acute hepatic
• Chronic hepatic
• Most are inherited diseases but some are acquired

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Biosynthesis of Heme
www.utmb.edu/pmch/Porphyria/Porphyria.jpg
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Gunthers Disease
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Congenital Erythropoietic Porphyria(Gunthers
Disease)
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• Rare recessive genetic disorder involving
  chromosome 10
• Lack of UROS (uroporphyrinogen III cosynthase)
  enzyme activity
• Results in build up of porphyrin isomers that the
  body cannot utilize
• Excess porphyrins UV light ? free radicals ?
  protein cross-
• linking and lipid peroxidation ? cell membrane
  damage and death

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Congenital Erythropoietic Porphyria(Gunthers
Disease) Mechanism
www.utmb.edu/pmch/Porphyria/Porphyria.jpg
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Signs Symptoms

• Photosensitivity resulting in burns and blisters
• Liver spleen enlargement
• Excessive hair growth
• Skin fragility blisters and erosions (face and
  fingers)
• Bone fragility due to bone marrow hypertrophy
• Redness/brown pigmentation of the teeth
• Blindness- retinal damage

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Fig.1 Scarring and hyperpigmentation of a person
with Gunthers Disease
1999 British Association of Dermatologists,
British Journal of Dermatology, 140, 573581
Fig.2 Blisters and erosions that result from UV
reaction with porphyrin isomers
Lim HW, Cohen JL. The Cutaneous Porphyrias.
Seminars in Cutaneous Medicine and Surgery 1999
Vo118, No 4 (December), 285-292.
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Diagnosis
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• Usually presents in the first days or weeks of
  life with severe photosensitivity
• Characteristic pink hue in urine
• Biochemical analysis detects increases in blood,
  fecal and urinary porphyrin levels
• Erythrocytes contain porphyrin isomers
• Difficult to diagnose because symptoms are
  general and may mimic other diseases
• Pre-natal diagnosis possible by genetic screening
  

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Treatment
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• Prevention and treatment of symptoms
• Complete avoidance of sun exposure in severe
  cases
• Photoprotective clothing
• UV A blocking sunscreens
• Oral administration of adsorbents ie. charcoal
  and cholestyramine
• Splenectomy
• Blood Transfusions
• Chemically induced bone marrow suppression by
  hydroxyurea ?reduces porphyrin synthesis
• Bone marrow transplantation

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Porphyria an urban legend???

• Theories exist that the original myth of vampires
  stemmed from porphyria
• Similarities between porphyria signs and symptoms
  and characteristics of vampires and werewolves
• Vampires sensitivity to light, red teeth and
  eyes
• Werewolves excessive hair growth, only come out
  at night (avoid sunlight)
• Today porphyrias are treated with blood
  transfusions, were vampires drinking blood to
  treat themselves?
• Prejudice against people with porphyria gave rise
  to the legends

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http//en.wikipedia.org/wiki/Porphyria
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Summary

• 4 pyrrole rings ? porphyrin ring Fe ? Heme
• Porphyrias are disorders caused by deficiency of
  enzymes in the synthesis of heme
• Two major cell types involved with heme
  synthesis erythroblasts (bone marrow),
  hepatocytes (liver)
• Type of porphyria can be classified as
  erythropoietic or hepatic
• Type of porphyria and its effects depends on
  which enzyme in the heme pathway is affected
• Congenital Erythropoietic Pophyria (Gunthers
  disease)
• A recessive genetic porphyria
• Lack of UROS enzyme leads to build up of useless
  porphyrin isomers
• Excess porphyrins in blood react with UV light
  forming free radicals and this leads to cell
  membrane damage
• Major symptoms include photosensitivity of skin
  (burning, blistering), red discolouration of
  teeth, excess hair growth, enlarged liver and
  spleen, bone weakness
• Common treatment involves avoidance of UV light
  and blood transfusions -other options available
  for more severe cases

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References

• Murphy G.M. The Cutaneous Porphyrias a Review.
  British Journal of Dermatology 1999 140
  573-581.
• Sassa Shigeru. Modern diagnosis and management of
  the porphyrias. British Journal of Haematology
  2006 135, 281292.
• Lim HW, Cohen JL. The Cutaneous Porphyrias.
  Seminars in Cutaneous Medicine and Surgery 1999
  Vo118, No 4 (December), 285-292.
• Berg JM, Stryer L, Tymoczko JL. Biochemistry 6th
  ed. New York, W.H. Freeman Company, 2007, pp.
  704-705.
• Kauppinen R. Porphyrias. Lancet 2005 365
  24152.