2. Porphyria
Done by: Nora al-kahtani
Hend al-Subai
Sumaiah al-Ghamdi
Submitted to : T. Nouf al Sultan
3. Contents:
• Disease Description
• Vampires and werewolves
• Culture and history
• Notable cases
• Mechanism of Heme synthesis
• Mechanism of prophyria
• Prophyria types
• Symptoms of Porphyria
• Diagnosis of Porphyria
• Treatment of Porphyria
4. Disease Description
• Porphyria is named from the ancient Greek
word porphura, meaning purple. The Greeks
borrowed the term from the Phoenicians,
who extracted a purple pigment from
purpura mollusks to dye the garments of
their royal family.
• a group of diseases that result from
abnormal accumulations of red and purple
pigments produced by the body, called
porphyrins.
5. Disease Description:
• The porphyrias are a group of rare inherited or
acquired disorders of certain enzymes that normally
participate in the production of porphyrins and
heme.
• They manifest with either neurological complications
or skin problems or occasionally both.
6. Vampires and werewolves
• There are at least eight types of porphyria, which
vary substantially in their symptoms and severity.
Historical victims of the worst, most disfiguring
forms may have inspired tales of werewolves and
vampires.
• some symptoms is hair growth, especially on the
face. , the hair growth can give the appearance of
a werewolf, leading to speculations that the myths
may have had a medical basis.
7. Vampires and werewolves
• The Symptoms including loss of facial
features and fingers, scarring of the
cornea and blindness. The condition
may have been less rare in the past,
especially in isolated area where
inbreeding could occur perhaps
giving rise to tales of vampires..
8. History : Notable cases
The mental illness exhibited by King George III
evidenced and no one diagnos it.1788
thirty-five years after his death, concluded he
suffered from acute mania. as a more likely
diagnosis.
1855
suggested manic-depressive psychosis as a more
likely diagnosis.
1941
The first suggestion that a physical illness was the
cause of King George's mental derangements came
in 1966, in a paper "The Insanity of King George III
1966
9. History :Notable cases
Porphyria in the Royal Houses of Stuart, Hanover and
Prussia".
were unconvinced. Many psychiatrists disagreed with
these diagnosis,
1968
British film based upon the 1991 Alan Bennett play, The
Madness of George III.
1994
was suggested that arsenic (which is known to be
porphyrogenic ) given to George III with antimony may
have caused his porphyria.
2005
10. History :Notable cases
• Queen of Scots – King George III's great-
great-great-great-great-grandmother – also
suffered from acute intermittent porphyria.
11. History :Notable cases
• Maria of Portugal or "Maria the Mad" due to
both her religious fervour and her acute
mental illness that made her incapable of
handling state affairs after 1792, is also
thought to have suffered from porphyria.
12. How
• What is the truth of prophyria ?
• How does it happen?
• When it happen?
• Why it is happen ?
• What the types of porphyria?
13. Mechanism of Heme synthesis
Heme is a vital molecule for all of the body's organs,
although it is most abundant in the blood, bone
marrow, and liver. Heme is a component of several
iron-containing proteins called hemoproteins,
including hemoglobin.
15. The first step in haem
synthesis is the combination of
succinyl CoA and glycine to
produce aminolevulinic acid
(ALA). This reaction is energy
dependent and so occurs in the
mitochondria.
Mechanism of Heme synthesis
16. Mitochondrial δ -aminolevulinic
acid (ALA) is transported to
the cytoplasm, where ALA
dehydratase (also called
porphobilinogen synthase)
dimerizes 2 molecules of ALA
to produce the pyrrole ring
compound porphobilinogen
(PBG).
Mechanism of Heme synthesis
17. • UPG III is converted to
coproporphyrinogen III (CPGIII) by
decarboxylation of the acetate side
chains under the influence of the
enzyme uroporphyrinogen
decarboxylase.
Mechanism of Heme synthesis
18. • CPGIII enters the mitochondria
where it converted to
protoporphyrinogen IX (PPG IX)
by an unknown mechanism. This
reaction is catalyzed by the
enzyme coproporhyrinogen
oxidase.
Mechanism of Heme synthesis
19. PPG IX is further converted
within the mitochondria to
protoporphrin IX.
Mechanism of Heme synthesis
20. • It only remains for the central
ferrous ion to be inserted to
complete the synthesis of haem.
This reaction is catalyzed by the
enzyme ferrochelatase and
requires the presence of reducing
agents.
Mechanism of Heme synthesis
22. Mechanism of prophyria
In humans, porphyrins are the main precursors of
heme, an essential constituent of hemoglobin,
myoglobin, catalase, peroxidase.
Heme synthesis—that some reactions occur in the
cytoplasm and some in the mitochondrion
23. Mechanism of prophyria
Deficiency in the enzymes of the porphyrin pathway leads to insufficient
production of heme. Heme function plays a central role in cellular
metabolism. This is not the main problem in the porphyrias; most heme
synthesis enzymes—even dysfunctional enzymes—have enough residual
activity to assist in heme biosynthesis.
24. Mechanism of prophyria
• The principal problem in these deficiencies is the
accumulation of porphyrins, the heme precursors, which
are toxic to tissue in high concentrations. The chemical
properties of these intermediates determine the location
of accumulation, whether they induce photosensitivity,
and whether the intermediate is excreted (in the urine
or feces)
25. Mechanism of prophyria
There are eight enzymes in the heme biosynthetic pathway, while the other
Defects in any of these can lead to some form of porphyria.
The hepatic porphyrias are characterized by acute neurological attacks
(seizures, psychosis, extreme back and abdominal pain and an acute
polyneuropathy), while the erythropoietic forms present with skin
problems, usually a light-sensitive blistering rash and increased hair
growth.
26. Type of Porphyria Deficient Enzyme
Main Location of
Porphyrin Buildup
delta-aminolevulinate-
dehydratase deficiency
porphyria
delta-aminolevulinic acid dehydratase liver
acute intermittent porphyria porphobilinogen deaminase liver
hereditary coproporphyria coproporphyrinogen oxidase liver
variegate porphyria protoporphyrinogen oxidase liver
congenital erythropoietic
porphyria
uroporphyrinogen III cosynthase bone marrow
porphyria cutanea tarda uroporphyrinogen decarboxylase (~75% deficiency) liver
hepatoerythropoietic
porphyria
uroporphyrinogen decarboxylase (~90% deficiency) bone marrow
erythropoietic
protoporphyria*
ferrochelatase (~75% deficiency) bone marrow
27. Symptoms of Porphyria
Porphyria is a group of disorders that can cause nerve or skin
problems.A porphyria that affects the skin is called cutaneous
porphyria.
A porphyria that affects the nervous system is called acute
porphyria.The most common type of porphyria is porphyria
cutanea tarda (PCT)
28. Acute Porphyria
Acute porphyrias include forms of the
disease that typically cause nervous system
symptoms, which appear quickly and can be
life-threatening. Acute porphyria attacks
are rare before puberty and after
menopause in women. Symptoms may last
one to two weeks and usually improve slowly
after the attack.
29. Symptoms of Acute Porphyria
Possible s Possible signs and symptoms of
acute porphyria include:
• Severe abdominal pain
• Swelling of the abdomen
• Constipation or diarrhea
• Vomiting
• Insomnia
• Heartbeat you can feel (palpitations)
• High blood pressure
• Anxiety or restlessnessMuscle pain,
tingling, numbness, weakness or paralysis
30. Symptoms of Acute Porphyria
• Red or brown urine
• Pain in extremities, back, chest,
neck, or head
• Loss or impairment of movement
• Respiratory paralysis
• Behavioral changes, including
agitation, confusion, hallucinations,
and depression.
• Convulsions, as a result of
excessive vomiting and/or diarrhea
• Increased heart rate
31. Cutaneous porphyrias
Cutaneous porphyrias include forms of the
disease thae skin symptoms as a result of
oversensitivity to sunlight, but these forms
don't usually affect your nervous system.
Attacks may last for several days. With
some forms, signs and st causymptoms may
start during infancy or childhood
32. Symptoms of Cutaneous porphyrias
• Possible signs and symptoms of
acute porphyria include:
• Sudden painful skin redness
(erythema) and swelling (edema)
• Blisters that take weeks to
heal
• Itching
• Scars or skin color changes from
healing blisters
• Increased hair growth
• Red or brown urine
33. Symptoms of Cutaneous porphyrias
• Sensitivity to sunlight
• Fragile skin
• Changes in skin color
• Anemia
• Teeth discoloration
• Bone fragility or bone loss, due
to Vitamin D deficiency
34. Diagnosis of Porphyria
• Blood, urine, and stool tests are performed
to diagnose porphyria. The best time to be
tested is during an outbreak of symptoms or
around the time of them.
• Sometimes multiple tests will be required
before the diagnosis of a particular type of
porphyria is possible. Because porphyria
often runs in families, other family members
can be tested and counseled after a positive
diagnosis
35. Treatment of Porphyria
Outbreaks of symptoms of acute porphyria
often require hospitalization. Patients may be
given medicine for pain, nausea, and vomiting.
They will also often receive glucose or hemin
(Panhematin) injections . Panhematin is the
only heme therapy approved for use in the U.S.
Severe attacks of acute porphyria can cause
lasting nerve damage and muscle weakness
that can take months to resolve. Treatment of
cutaneous porphyria depends on the specific
type and the severity of the symptoms.
36. Treatment of Porphyria
Treatment of porphyria cutanea tarda
includes:
• Regular blood removal (phlebotomies) to
reduce the amount of iron in the liver
• Low doses of the antimalarial drug
chloroquine or hydroxychloroquine
• Avoidance of triggers
• Treatment of any underlying condition
such as HIV or hepatitis C
37. treatment of porphyria cutanea tarda
with chloroquine
Twenty men and one woman with porphyria
cutanea tarda were treated with oral
chloroquine, 125 mg twice weekly.In nineteen of
the patients chloroquine was taken for 8–5
months on average before complete clinical and
biochemical remission occurred. Initially,
treatment led to a considerable increase in
urinary uroporphyrin and a mild increase in serum
transaminases, but no adverse clinical reactions
were observed. As the mechanism of chloroquine
action in porphyria cutanea tarda has not yet
been clarified, special caution must be observed
when it is used therapeutically.
