Porphyrias

9 types of porphyria‫فيه‬
‫ انزيم بسبب انه في واحد فيهم مشترك اسمه‬8 ‫ بيحصل في‬defect ‫لكن ال‬

Uroporphrinogen decarboxylase ‫بهيب‬
PCT HEP
AD AR
 All types are inherited except one type is acquired= PCT

Classification
 According to site of expression of deficient enzyme (1ry site
of over production of porphyrin)
  

erythropoietic Hemopoietic hepatic

 Congenital erythropioteic P HEP AIP

 Erthyropioteic protoporphyria VP
X linked HCP
PCT

CEP=congenital erythropoietic porphyria

HEP=hepatoerthyropoietic porphyria
AIP=acute intermittent porphyria
VP=variegate porphyria
HCP=hereditary coproporphyria PCT=porphyria cutanea tarda
AIP,ALA dehydrogenase deficiency ‫ماعدا‬cutaneous ‫كلهم‬
‫و انواع خفيفة الن في‬severe bulla scar ‫ليه في انواع فيها‬
 types of cellular damage depend on stability of tissue distribution of
porphyrin
 
Water soulable porphyrin lipid soulable porphyrin
Uroporphyrin protoporphyrin
coproporphyrin 
 more affinity to lipid memb,
Diffusion,acummlation in the skin erythema,burning,irritation
Vesicles,bullae,milia.hypertrichosis minimal bullae& scarring

Porphobilinogen excreted in urine

ALAexcreted in urine
uroporphrinogen in urine
coproporphyrinin stool
protoporphyrinogenstool

Histopathology of porphyria:-except AIP&ALA dehydrogenase

‫عبارة عن ايه‬bullae ‫الفكرة انه هيباي فيه‬defiency no skin affection,
1. Subepidermal cleft
2. Dermal papillae extend from floor of bulla into bulla cavity(festooning) ‫شبه ال‬
fistula
3. Hyaline material are present within papillary dermis, many extend into deep
dermis
4. Hyaline depositsrepresent collagen IV
PAS +VE
disastase resistant

ecrine ‫و‬hair follicle ‫ حوالين‬hyline deposits ‫ بس الفرق ان‬lipid protoniosis ‫اخر نقطة هي نفس‬
gland
5.DIF:IgG(rarlyIgM)+C3+fibrin deposits in
 
Wall of blood vessels DEJ
 ‫ ليه البورفريا انتشرت في مصر والدول االروبية‬:‫سؤال شفوي‬
 HCV
Alcoholic liver
Wine consumption

Pathophysiology:
Mutation in any of the genes encoding the enzymes in the heme biosynthsis pathway

Acummlation of circulating porphyrin in the blood&or porphyrin precursors

Reach the skin

Porphyrins absorb light easily intensely in (400-410 nm) penetrate window glass

Major window peak

Photo activated porphyrin enter in the excited state
 transfer their absorbed energy to
 Oxygen molecule
O2

Creating reactive oxygen species
‫هي دي اللي بتدمر الجلد‬
Singlet o2 & free radicals 
Subsequent lipid perioxdation,pentrate cell linkage

Cellular& tissue damage
‫النهم‬sun block ‫هياثر عليه ومش هينفع معاه اي‬visible light ‫مشكلة العيان مش التعرض الشعة الشمس أل اي‬
physical agents ‫مفيش قدام العيان ده غير‬uvb ‫او‬uva ‫بيشتغلو علي‬
 photosenstivity‫اول ما العيان ما يتعرض للشمس‬

Erythema,burning,vesicles (heal with scarring),bullae
with chronic exposuremillia, hyperpigmentation, hypertrichosis, deformity
‫وشه مكرمش وفيه شعر جامد شبه الذئب‬
NO photosensitivity in AIP &ALA dehydratase defiencybecause porphyrias are
bond as zinc complexes in heme protein not deposited in free form in skin
ALA dehydratase defiency defective enzyme act early on heme biosynthesis
(ALA)is not phototoxic porphyrin precursor(bind to zinc complex)
Normally: small amount of porphyrin excreted in urine& stool
ALL porphyrias are red in colorshow intense flurence with wood’s light

‫والسؤال بتاعها اللي جه في االمتحان‬heme , ‫في جملة سابه يكب ال‬heme synthesis‫اختصار خطوات ال‬
Mention process,diseases caused by each defect
 Since birth  Congenital erythropoietic porphyria skin
  water soluable
blood erythropoietic
Gunther’s disease mode of inhertence AR
Enzyme defect uroporpherinogen III cosynthase defectnon enzymatic reaction

 uroporphyrin I
Coproporphyrin I can’t participate in heme synthesisACUMMLATE MASSIVE
RBCSHEMOLYSIS

CP:
Start in infancy
 
skin: as HEP - SYSTEMICabnormal RBCshemolysis
SEVERE - variant degree of haemolytic anemia
Mutilation,ulceration 
Deformities in hands splenomegaly hyperspleenism
Nail amyloidosis -eye
Pseudosclerotic changes dd :PCT -teetherythrodontia(red teeth éred flurence
On exposure to uvwood’s light
-bone:deposition of porphyrin in bone

Deformity
How to confirm the diagnosis:
Urine: uroporphyrin I pink color
+coprporphyin I stung red
Stool: coprporphyin I
Blood :red flurence due to  uroporphyrin I

Pink or reddish staining of the diaper is an early clue for diagnosis

Treatment:
-Skin photoprotection
-Specific:splenectomy
Bone marrow transplantation
-Regular blood transfusionmain polycythemia

 
Correct severe anemia -- erythropoiesis

-- Hb production porphyria
Disadvantage ; iron overload so concomitant intake desfmoxamine
-IV hematin in late stage overproduction of porphyrin precursors via -ve feedback
mechanism (inhibit activity of rate limiting enzyme in hemebiosynthesis ALA
synthesis
X linked dominant protoporphyria Erthyropoiteic protoporphyria

Enzyme X linked dominant AD 2nd highest incidence after PCT for

defect ALA synthase enzyme cutaneous porphyria
childhood

lab protoporphyrin (water insoluable)lipid

soluable
Pin RBCstransient redflurencevanish
Pin stool
Not in urine

C.P THE SAME Lipid solulable photosenstivity (mild)

edema,burning,erythema
during summer,spring
Minimal scarring&bullae in sun exposed
areas
NO erythodentia
systemic Liver disease more More systemic manifestations

H/P Largest esinophlic deposits in skin lesions

treatment
Photoprotection

Beta carotene
Cholrytramine
Narrow band uvb