1. Porphyrias: a review and case report

2. Anemia
MCV=HCT/RBC
80-100<80 >100
Microcytic Sudden massive blood lose
Marrow failure hemolysis
Megaloblastic anemia
Spurious macrocytic anemia

3. Microcytic anemia
Defect in hemoglobin synthesis
3-dimensional structure of hemoglobin. The four subunits
are shown in red and yellow, and the heme groups in
green.

4. Microcytic anemia
Defect in hemoglobin sythesis
Iron binding capacityLow or normal High
High Low or normalIron
Iron deficiency
Defect in:
Porphyrin synthesis
Heme synthesis
Globin synthesis

5. Defect in:
Porphyrin synthesis
Heme synthesis
Globin synthesis
Hemoglobin electrophoresis
AbnormalNormal
Defect in:
Porphyrin synthesis
Heme synthesis
Defect in:
Globin synthesis
Quantitative QualitativeBoth
Thalassemia Sickle-thal S,C,F,ect

6. Heme
Non-erythroid Erythroid
Haemoproteins Haemoglobin
Electron transfer and energy trapping
myoglobin Cytochromes Others

7. Porphyrins synthesis
URO I
Spontaneous
COPRO I
Mitochondrion Cytosol

8. ALA synthase
D-ALA
ALA dehydrase
PBG deaminase
Hydroxymethylbilane
NH2-CH2-COOH+
Glycine
PBG
Water-soluble
Excreted in urine
Water-soluble
Excreted in urine

9. Hydroxymethylbilane
Uroporphyrinogen III
URO I
URO III synthase Spontaneous
Coproporphyrinogen III
COPRO I
URO III
decarboxylase
Less water-soluble
Excreted in urine/feces
Water-soluble
Excreted in urine

10. CORPO III
Protoporphyrinogen IX
COPRO oxidase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Poor water-solubility
Excreted in feces

11. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
(Neurological
Porphyrias)
(Cutaneous
Porphyrias)
(Unstable)
Main Types of Porphyria

12. Main Types of Porphyria
Acute
Porphyrias
Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Erythropoietic Protoporphyria
(Neurological
Porphyrias)
(Cutaneous
Porphyrias)
InheritanceTissue expression
Liver
Erythroid cells
E , L
Autosomal recessive
Liver
Liver
Liver
Liver
Autosomal dominant
Autosomal dominant
Autosomal dominant
Autosomal dominant
Autosomal dominant
Autosomal recessive

13. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
Erythropoietic Protoporphyria

14. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine

15. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine
Urine
feces
urine

16. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic Porphyria
Non-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine
Urine
feces
feces
urine

17. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic PorphyriaNon-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Urine
Urine
Feces

18. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic PorphyriaNon-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
urine Urine
Urine
Feces

19. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic PorphyriaNon-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Feces
Feces

20. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic PorphyriaNon-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Feces
Feces
urine
Urine
Feces
Zn-protoporphyrin

21. Acute
Porphyrias Acute Intermittent Porphyria
Variegate Porphyria
Hereditary Coproporphyria
Porphyria Cutanea Tarda
Congenital Erythropietic PorphyriaNon-acute
Porphyrias
ALAD Deficiency Porphyria
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Glycine +Succinyl CoA
ALA synthase
ALA
ALA dehydrase
PBG
PBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO III
COPRO I
PROTO IX
COPRO oxidase
URO III
decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Zn-protoporphyrin

22. Hepatic Porphyrias (normal RBC Porphyrins) Erythropoietic Porphyrias (↑ RBC Porphyrins)
Acute Intermittent Porphyria (AIP) Congenital Erythropoietic Porphyria (CEP)
Variegate porphyria (VP) Erythropoietic Protoporphyria (EP)
Hereditary Coproporphyria (HCP)
Porphyria Cutanea Tarda (PCT)
Sunnybrook Health Sciences Center Sampling Guide
Presentation: Porphyrias Tests to order Sample
Acute symptoms AIP 1. Urine Porphyrin Precursors Screen & Quantitation Random (50 ml) or 24-h with Tartaric acid
Acute symptoms
+ skin lesions
(may occur
independently)
VP
HCP
2. Feces Porphyrins Screen & Quantitation Random
Skin lesions PCT
CEP
EP
1. Urine Porphyrin Precursors Screen & Quantitation
2. Feces Porphyrins Screen & Quantitation
3. Urine Porphyrins Screen & Quantitation
4. RBC Porphyrins Screen & Quantitation
Random (50 ml) or 24-h with Tartaric acid
Random
Random (50 ml) or 24-h with Na2CO3
Lavender-top (EDTA) blood; need Hct
Notes:
At time of acute attack:
1. Collect a random urine sample first (50 ml with no preservatives), before attempting to collect a 24-h sample.
2. Request "Porphyrin Precursors" (ALA & PBG) instead of "Porphyrins" screen and quantitation. The Laboratory will
have to adjust pH to 4-6 for "Porphyrin Precursors", but pH 8-10 for "Porphyrins". - The commonest problem causing
confusion!
3. All sample containers should be covered with tin foil to shield off from light.

24. Test Name Specimen Type Search / Alternate Name
Porphyrin
Precursors (ALA & PBG)
Urine (24h)
ALA,Aminolevulinic Acid,PBG,Porphobilinogen, -ALA,
-aminolevulinic Acid
Porphyrin
Precursors (ALA & PBG)
Urine (Random)
ALA,Aminolevulinic Acid,PBG, -ALA,Porphobilinogen
Porphyrins:
Quantitation
Urine (24h) Uroporphyrin,Heptacarboxylic Acid,Hexacarboxylic
Acid,Pentacarboxylic Acid,Coproporphyrin
Porphyrins:
Quantitation
Urine (Random) Uroporphyrin,Heptacarboxylic Acid,Hexacarboxylic
Acid,Pentacarboxylic Acid,Coproporphyrin
Porphyrins:
Quantitation
Whole blood
(EDTA) Free Protoporphyrin,Protoporphyrin - Free
Porphyrins:
Quantitation
Feces (Random) Coproporphyrin,Uroporphyrin,Heptacarboxylic
Acid,Hexacarboxylic Acid,Pentacarboxylic
Acid,Deuteroporphyrin,Mesoporphyrin,Protoporphyrin
Porphyrins:
Quantitation
Plasma (EDTA
or Heparin)
Uroporphyrin,Heptacarboxylic Acid,Hexacarboxylic
Acid,Pentacarboxylic Acid,Coproporphyrin
Bio-Rad
Column
HPLC
Porphyrin assays provided through HICL

25. Isocoproporphyrin Not Available
- See Note.
Porphobilinogen
Deaminase
Whole blood
(Heparin)
Uroporphyrinogen 1
Synthetase,HMB,Hydroxymethylbilane Synthase
Porphyrins
: Screen
Urine (24h)
Porphyrins:
Screen
Feces
(Random)
Porphyrins:
Screen
Urine
(Random)
Zinc
Protoporphyrin
Whole blood
(Heparin) ZPP,Metal
ICP-MS
Lead Whole blood
(heparin)
Pb,Zinc Protoporphyrin,ZPP,Metal
Enzymatic
Spectrophometric
Screening

26. CASE
A boy, average hematologic parameters over the subsequent 3 years were as
follows:
Defect in:
Porphyrin
synthesis
Heme synthesis
Globin synthesis
microcytic
Iron studies were unremarkable →
Hemoglobin (Hb) level, 70.0 g/L;
Mean corpuscular volume (MCV), 67 fL →
Mean corpuscular hemoglobin level, consistently < 20 pg;
Reticulocyte counts ranged from 3.6% to 6.7%;

27. A physical examination revealed scars on the face, hands, and
forearms. → photosensitive bullous dermatosis
A 50-mL urine sample contained 2003 ug uroporphyrin (normal,
trace); 92% of this was uro-I. → CEP
The diapers exhibited brilliant pink fluorescence when illuminated with
long-range ultraviolet light. → Photosensitive porphyrin rings
Fluorescent red cells were detected using a microscope fitted with a
405 nm light source. → CEP or EP
Erythrocyte UROS activity was 21% of the normal mean.
Collectively, these findings confirmed the diagnosis of CEP.

28. Erythrocyte UROS activity was normal in both parents, an unexpected finding
as obligate carriers (heterozygotes) for UROS mutations generally have half-
normal enzymatic activity.
UROS was sequenced, and no mutations or deletions were found in the
child or the parents.
A GATA1 point mutation was found in the child at codon 216, changing
arginine to tryptophan (R216W), as well as on 1 of the 2 GATA1 alleles of his
mother and maternal grandmother.
GATA1 gene, at Xp11.23, encodes a transcription factor, GATA binding
factor 1 (GATA-1), that is critical for normal erythropoiesis, globin
gene expression, and megakaryocyte development.
GATA-1 also regulates expression of UROS in developing erythrocytes.

29. General Symptomology:
__Abdominal pain
___Abdominal tenderness
___Loss of appetite
___Nausea
___Vomiting
___Constipation
___Carbohydrate craving
___Breast secretions
___Diarrhea
___Partial ileus [Intestinal blockage]
___Abdominal distention
___Dysuria [Painful Urination]
___Bladder Dysfunction
___Urinary Retention
___Amenorrhea [Lack of menses]
Physical Findings of Acute Attack
__Red or dark urine
___Tachycardia [Pulse] >100
___Labile hypertension >90 diastolic [blood pressure]
___Fever [Pyrexia]
___Profused sweating
___Edema [Retention of fluids] [Swelling]
___Postural Hypotension [Low Blood Pressure]
___Hypertrichosis [excessive body hair growth]
___Hyperpigmentation [skin coloring]

30. Neurological Symptoms of Acute Attack
[Peripheral manifestations]
___Peripheral neuropathy
___Muscle weakness
___Paresis . paralysis
___Sensory disorde
___Respiratory paralysis
___Foot drop
___Wrist drop
___Abnormal Gait
___Pain: Arms, legs, hips and/or lower back
___Loss of sensation
___Dyesthesia
___Numbness
___Tingling
___Burning Sensation
___Bulbar paresis
___Tongue paralization
___Mouth paralization
___Throat paralization
[Cerebral manifestations]
___Behavorial change
___Anxiety
___Irritability
___Delirium
___Depression
___Confusion
___Hallucination
___Insomnia
___ANS [altered neurological state]
___Restlessness
___Sensory loss
___Seizure
___Depressed or absent tendon reflexes
___Cranial nerve involvement

31. Hematology/Blood Chemistry
___Hyponatremia [Below normal sodium level] <130
___Increased Bun [Urea Nitrogen]
___Increased AST [Aspartate Aminotransferase]
___Elevated Alkaline Phosphatase [Liver panel test]
___Increased ALT [Aspartate Aminotransferase]
___Hypokalemia [Below normal potassium level]
___Leukocytosis [Abnormal increase in WBC] > 10,000
___Increased ESR >22
___Hypochloremia < 90 [A decrease in the chloride level]
___Anemia [Iron deficiency]
Cutaneous manifestations
___Skin photosensitivity
___Blistering
___Severe Tissue Scarring
___Increased Hair growth
___Pigmentation Darkening
___Thickening of skin
___Severe Itching
Special lab studies
___Decreased blood volume
___EEG abnormalities
___Electromyographic abnormalities
___Muscle denervation
___Decreased nerve conduction velocity
___Abnormal CSF
___Increased fibrillation potential