Transcript Porphyria-R - Lab Test Consult

Porphyrias: a review and case report
Anemia
MCV=HCT/RBC
<80
80-100
Microcytic
Sudden massive blood lose
Marrow failure hemolysis
>100
Megaloblastic anemia
Spurious macrocytic anemia
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.
Microcytic anemia
Defect in hemoglobin sythesis
Low or normal
High
Defect in:
Porphyrin synthesis
Heme synthesis
Globin synthesis
Iron binding capacity
Iron
High
Low or normal
Iron deficiency
Defect in:
Porphyrin synthesis
Heme synthesis
Globin synthesis
Hemoglobin electrophoresis
Normal
Abnormal
Defect in:
Porphyrin synthesis
Heme synthesis
Defect in:
Globin synthesis
Quantitative
Both
Qualitative
Thalassemia
Sickle-thal
S,C,F,ect
Heme
Non-erythroid
Erythroid
Haemoproteins
Haemoglobin
Electron transfer and energy trapping
myoglobin
Cytochromes
Others
Porphyrins synthesis
Mitochondrion
Cytosol
Spontaneous
URO I
COPRO I
Glycine
+
NH2-CH2-COOH
ALA synthase
D-ALA
Water-soluble
Excreted in urine
ALA dehydrase
PBG deaminase
PBG
Hydroxymethylbilane
Water-soluble
Excreted in urine
Hydroxymethylbilane
URO III synthase
Spontaneous
URO I
Uroporphyrinogen III
COPRO I
URO III
decarboxylase
Water-soluble
Excreted in urine
Coproporphyrinogen III
Less water-soluble
Excreted in urine/feces
CORPO III
COPRO oxidase
Protoporphyrinogen IX
Poor water-solubility
Excreted in feces
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Main Types of Porphyria
Acute
Porphyrias
(Neurological
Porphyrias)
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane (Unstable)
Non-acute
Porphyrias
(Cutaneous
Porphyrias)
Porphyria Cutanea Tarda
URO III synthase
Erythropoietic Protoporphyria
Congenital Erythropietic Porphyria
Spontaneous
URO III
URO I
URO III
decarboxylase
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
COPRO I
Main Types of Porphyria
Tissue expression
Inheritance
Liver
Autosomal recessive
Liver
Autosomal dominant
Liver
Autosomal dominant
Variegate Porphyria
Liver
Autosomal dominant
Porphyria Cutanea Tarda
Liver
Autosomal dominant
Erythropoietic Protoporphyria
E,L
Autosomal dominant
ALAD Deficiency Porphyria
Acute
Porphyrias
Acute Intermittent Porphyria
(Neurological
Porphyrias) Hereditary Coproporphyria
Non-acute
Porphyrias
(Cutaneous
Porphyrias)
Secondary
Porphyrias
Congenital Erythropietic Porphyria
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Erythroid cells
Autosomal recessive
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
urine
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
Porphyria Cutanea Tarda
URO III synthase
Erythropoietic Protoporphyria
Congenital Erythropietic Porphyria
Spontaneous
URO III
URO I
URO III
decarboxylase
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
urine
ALA dehydrase
Hereditary Coproporphyria
Variegate Porphyria
PBG
PBG deaminase
urine
Hydroxymethylbilane
Non-acute
Porphyrias
Porphyria Cutanea Tarda
URO III synthase
Erythropoietic Protoporphyria
Congenital Erythropietic Porphyria
Spontaneous
URO III
URO I
URO III
decarboxylase
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
urine
ALA dehydrase
Hereditary Coproporphyria
Variegate Porphyria
PBG
PBG deaminase
urine
Hydroxymethylbilane
Non-acute
Porphyrias
Porphyria Cutanea Tarda
URO III synthase
Erythropoietic Protoporphyria
Congenital Erythropietic Porphyria
urine
Spontaneous
URO III
URO I
URO III
decarboxylase
UrineCOPRO III
feces
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
urine
ALA dehydrase
Hereditary Coproporphyria
Variegate Porphyria
PBG
PBG deaminase
urine
Hydroxymethylbilane
Non-acute
Porphyrias
Porphyria Cutanea Tarda
URO III synthase
Erythropoietic Protoporphyria
urine
Spontaneous
URO III
URO I
URO III
decarboxylase
Congenital Erythropietic Porphyria
UrineCOPRO III
feces
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
feces
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
URO III synthase
Spontaneous
Congenital Erythropietic Porphyria
Porphyria Cutanea Tarda
Erythropoietic Protoporphyria
URO III
URO I
URO III
decarboxylase
Urine
COPRO I
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Urine
Feces
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
URO III synthase
Spontaneous
Congenital Erythropietic Porphyria
Porphyria Cutanea Tarda
Erythropoietic Protoporphyria
urine
URO III
URO I
URO III
decarboxylase
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Urine
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
COPRO I
Urine
Feces
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
URO III synthase
Spontaneous
Congenital Erythropietic Porphyria
URO III
Porphyria Cutanea Tarda
URO I
URO III
decarboxylase
Erythropoietic Protoporphyria
COPRO III
COPRO oxidase
Secondary
Porphyrias
Lead Poisoning
Feces
Iron Deficiency
Coproporphyrinuria
Feces
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
urine
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
URO III synthase
Congenital Erythropietic Porphyria
URO III
Porphyria Cutanea Tarda
Erythropoietic Protoporphyria
Secondary
Porphyrias
Spontaneous
Lead Poisoning
URO III
decarboxylase
Urine
Feces
Feces
Iron Deficiency
Coproporphyrinuria
URO I
Feces
COPRO III
COPRO oxidase
PROTO IX
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Zn-protoporphyrin
Heme
COPRO I
Acute
Porphyrias
Glycine +Succinyl CoA
ALAD Deficiency Porphyria
ALA synthase
Acute Intermittent Porphyria
ALA
ALA dehydrase
Hereditary Coproporphyria
PBG
Variegate Porphyria
PBG deaminase
Hydroxymethylbilane
Non-acute
Porphyrias
URO III synthase
Spontaneous
Congenital Erythropietic Porphyria
URO III
Porphyria Cutanea Tarda
URO I
URO III
decarboxylase
Erythropoietic Protoporphyria
COPRO III
COPRO oxidase
Secondary
Porphyrias
PROTO IX
PROTO oxidase
Lead Poisoning
Iron Deficiency
Coproporphyrinuria
Protoporphyrin IX
Ferrochelatase
Zn-protoporphyrin
Heme
COPRO I
Sunnybrook Health Sciences Center Sampling Guide
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)
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.
Porphyrin assays provided through HICL
Bio-Rad
Column
HPLC
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)
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)
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
ALA,Aminolevulinic Acid,PBG, -ALA,Porphobilinogen
Free Protoporphyrin,Protoporphyrin - Free
Enzymatic
Spectrophometric
Screening
Isocoproporphyrin
Not Available
- See Note.
Porphobilinogen
Deaminase
Whole blood
(Heparin)
Porphyrins:
Screen
Urine (24h)
Porphyrins:
Screen
Feces
(Random)
Porphyrins:
Screen
Urine
(Random)
Zinc
Protoporphyrin
Whole blood
(Heparin)
Lead
Whole blood
(heparin)
Uroporphyrinogen 1
Synthetase,HMB,Hydroxymethylbilane Synthase
ZPP,Metal
ICP-MS
Pb,Zinc Protoporphyrin,ZPP,Metal
CASE
A boy, average hematologic parameters over the subsequent 3 years were as
follows:
Mean corpuscular volume (MCV), 67 fL →
Iron studies were unremarkable →
microcytic
Defect in:
Porphyrin
synthesis
Heme synthesis
Globin synthesis
Hemoglobin (Hb) level, 70.0 g/L;
Mean corpuscular hemoglobin level, consistently < 20 pg;
Reticulocyte counts ranged from 3.6% to 6.7%;
A physical examination revealed scars on the face, hands, and
forearms. → photosensitive bullous dermatosis
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
A 50-mL urine sample contained 2003 ug uroporphyrin (normal,
trace); 92% of this was uro-I. → CEP
Erythrocyte UROS activity was 21% of the normal mean.
Collectively, these findings confirmed the diagnosis of CEP.
Erythrocyte UROS activity was normal in both parents, an unexpected finding
as obligate carriers (heterozygotes) for UROS mutations generally have halfnormal 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.
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]
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
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
Special lab studies
___Skin photosensitivity
___Blistering
___Severe Tissue Scarring
___Increased Hair growth
___Pigmentation Darkening
___Thickening of skin
___Severe Itching
___Decreased blood volume
___EEG abnormalities
___Electromyographic abnormalities
___Muscle denervation
___Decreased nerve conduction velocity
___Abnormal CSF
___Increased fibrillation potential