porphyria mbbs bds 1st year neet pg prep.pdf

Porphyria rep

1. DISORDERS OF HEME
SYNTHESIS
PORPHYRIAS

4. PORPHYRIAS
•Definition
A group of disorders associated with abnormalities in
biosynthetic
pathway of heme.
•Increased production & excretion of porphyrins or their
precursors

5. CLASSIFICATION
1.Congenital or Acquired
2. Acute or Chronic
3. Hepatic , Erythropoietic or Both
Whether the enzyme deficiency occur in
erythropoietic cells of BM or liver

6. Porphyrias
PORPHYRIA ENZYME DEFECT TYPE
ACUTE INTERMITTENT
PORPHYRIA (AD)
PORPHOBILINOGEN
DEAMINASE
HEPATIC
CONGENITAL ERYTHROPOEITIC
PORPHYRIA (AR)
UPG III SYNTHASE ERYTHOPOETIC
PORPHYRIA CUTANEA TARDA
(AD)
UPG DECARBOXYLASE HEPATIC
HEREDITARY
COPROPORPHYRIA (AD)
CPG OXIDASE HEPATIC
VARIEGATE PORPHYRIA (AD) PPG OXIDASE HEPATIC
ERYTHROPOIETIC
PROTOPORPHYRIA (AD)
FERROCHELATASE ERYTHROPOETIC

8. •Visible light at 400 nm “excites” porphyrin, then they
react with molecular O2
•Free radicals generated, injure lysosomes
-skin damage, scarring

9. ALA
Synthase
ALAS deficiency

10. ALAS deficiency
•(Not actually a porphyria)
• X-linked sideroblastic anemia
•Sideroblasts are erythroblasts with non heme iron
containing organelles called siderosomes
Red cell count decreased
•Hemoglobin decreased

11. ALA
dehydratase
ALA dehydratase
deficient porphyria

12. ALA dehydratase deficient porphyria (Doss
porphyria)
• Rare
•Abdominal pain
•Neuropsychiatric signs
•Urinary ALA increased
•Differential diagnosis is lead poisoning
Tyrosinemia type 1

13. PBG
deaminase
Acute Intermittent
Porphyria

14. Acute intermittent porphyria
•Defect in hydroxymethylbilane synthase or
porphobilinogen deaminase or UPG I synthase
•Most common acute porphyria
•Accumulating intermediate is Porphobilinogen (PBG)

15. Manifestations:
•Acute abdominal pain
•Vomiting
•Abdominal distention
•Neurological manifestations like sensory and motor
disturbances, confusion and agitation

16. •Behavioural changes (Irritability, insomnia,
emotional lability)
•Fluctuating blood pressure
•Tachycardia (Resting heart beat >100 beats per
minute)
•NO Photosensitivity (Why? Because
photosensitivity is caused by accumulation of
intermediates which are formed after HMB)

17. Acute attacks are provoked by:
•Drugs like barbiturates
•alcoholic beverages
•endocrine factors
•calorie restriction
•Stress
•Infections
Usually resolve within two weeks

18. Biochemical findings
•Increased excretion of ALA and PBG in urine
•Absence of porphyrins (uroporphyrin and
coproporphyrin) in urine and stools
•Watson-Schwartz test (detect PBG)

19. •During acute attack the urine is
colorless
•On prolonged light exposure
color changes to pink due to
photo-oxidation of PBG to
porphobilin
•Urine should be collected freshly
and transported in dark bottles

20. •Treatment
Currently liver directed gene therapy with
Adeno Associated Viral vector has been proven to
prevent drug induced AIP

21. Congenital
Erythropoietic
Porphyria
UPG III
synthase

22. Congenital Erythropoietic Porphyria
• UPG 111 synthase defect
•In this condition type 1 isomer is formed considerably,
they are converted in to porphyrins type 1

24. Clinical features
Severe cutaneous
photosensitivity
Skin blistering

25. Repeated attacks of dermatitis lead
to facial deformities
•Monkey facies.
•Mimic leprosy
•Mutilation of nose, ear and
cartilage

26. •Erythrodontia- when UV light is
reflected on to teeth red
fluorescence
•Port wine coloured urine(dark
red)

27. Lab findings
•Plasma uroporohyrin I ++
coproporphyrin I ++
•Urine
•Feces
•Prenatal diagnosis by porphyrin in amniotic
fluid , URO synthase enzyme activity in
chorionic villus and cultured amniotic cells

28. Treatment
•Gene therapy
•Beta carotene to protect from sunlight

29. Porphyria cutanea tarda
UPG
decarboxylase
Porphyria cutanea
tarda

30. Porphyria Cutanea Tarda
• Most common porphyria
•UPG decarboxylase deficiency
•80% acquired attributed to UPG Decarboxylase
inhibitors

31. Manifestations
•Cutaneous photosensitivity and blisters
•ALA and PBG accumulation can lead to
neurovisceral manifestations

32. Lab findings
•Plasma
urine
uroporphyri
n++

33. Hereditary
Coproporphyria
CPG
Oxidase
Hereditary
Coproporphyria

34. Hereditary Coproporphyria
•CPG oxidase defect
•Symptoms similar to AIP but milder.
•Photosensitivity
•ALA and PBG get accumulated
•UP and CP excreted in urine and feces

35. PPG
Oxidase
Porphyria
Variegata

36. Porphyria Variegata
•PPG oxidase deficiency
•Acute abdominal pain
•Neuropsychiatric manifestations
•Photosensitivity
•ALA
PBG urine
Coproporphyrin III
•Protoporphyrin III - feces

37. Erythropoietic
protoporphyria
Ferrochelat
ase

38. Erythropoietic protoporphyria
•Deficiency of enzyme ferrochelatase
•Most common porphyria in children
•Non blistering photosensitivity
•Protoporphyrin increased in plasma ,RBC and feces

40. •Most common acute porphyria
•Most common porphyria
•Most common porphyria in children
•Enzyme deficiency in PCT and AIP
•Confirmatory diagnostic test for all porphyrias are enzyme
analysis and
mutation analysis
•First line investigation of porphyrias with neurovisceral
symptoms is
spot urine ALA and PBG
•First line investigation of porphyrias with photosensitivity is
plasma
porphyrins