porphyrias: a review and case report. anemia mcv=hct/rbc 80-100 100 microcytic sudden massive blood...
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Porphyrias: a review and case report
Anemia
MCV=HCT/RBC
80-100<80 >100
Microcytic Sudden massive blood loseMarrow failure hemolysis
Megaloblastic anemiaSpurious 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
Iron binding capacityLow or normal High
High Low or normalIron
Iron deficiencyDefect in:Porphyrin synthesisHeme synthesisGlobin synthesis
Defect in:Porphyrin synthesisHeme synthesisGlobin synthesis
Hemoglobin electrophoresis
AbnormalNormal
Defect in:Porphyrin synthesisHeme synthesis
Defect in:Globin synthesis
Quantitative QualitativeBoth
Thalassemia Sickle-thal S,C,F,ect
Heme
Non-erythroid Erythroid
Haemoproteins Haemoglobin
Electron transfer and energy trapping
myoglobin Cytochromes Others
Porphyrins synthesis
URO ISpontaneous
COPRO I
Mitochondrion Cytosol
ALA synthase
D-ALA
ALA dehydrase
PBG deaminase
Hydroxymethylbilane
NH2-CH2-COOH+
Glycine
PBG
Water-solubleExcreted in urine
Water-solubleExcreted in urine
Hydroxymethylbilane
Uroporphyrinogen III
URO I
URO III synthase Spontaneous
Coproporphyrinogen III
COPRO I
URO III decarboxylase
Less water-solubleExcreted in urine/feces
Water-solubleExcreted in urine
CORPO III
Protoporphyrinogen IX
COPRO oxidase
PROTO oxidase
Protoporphyrin IX
FerrochelataseHeme
Poor water-solubilityExcreted in feces
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
(NeurologicalPorphyrias)
(CutaneousPorphyrias)
(Unstable)
Main Types of Porphyria
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
(NeurologicalPorphyrias)
(CutaneousPorphyrias)
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
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
Erythropoietic Protoporphyria
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO IIIdecarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine
Urinefeces
urine
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO IIIdecarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
urine
urine
Erythropoietic Protoporphyria urine
Urinefeces
feces
urine
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO IIIdecarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Urine
UrineFeces
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
urine Urine
UrineFeces
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO IIIdecarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Feces
Feces
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Feces
Feces
urine
UrineFeces
Zn-protoporphyrin
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
ALAALA dehydrase
PBGPBG deaminase
Hydroxymethylbilane
URO III URO I
URO III synthase Spontaneous
COPRO IIICOPRO I
PROTO IX
COPRO oxidase
URO III decarboxylase
PROTO oxidase
Protoporphyrin IX
Ferrochelatase
Heme
Erythropoietic Protoporphyria
Zn-protoporphyrin
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)
VPHCP
2. Feces Porphyrins Screen & Quantitation Random
Skin lesions PCTCEPEP
1. Urine Porphyrin Precursors Screen & Quantitation2. Feces Porphyrins Screen & Quantitation3. Urine Porphyrins Screen & Quantitation4. RBC Porphyrins Screen & Quantitation
Random (50 ml) or 24-h with Tartaric acidRandom Random (50 ml) or 24-h with Na2CO3Lavender-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.
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
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
CASE
A boy, average hematologic parameters over the subsequent 3 years were as follows:
Defect in:Porphyrin synthesisHeme synthesisGlobin 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%;
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.
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 thechild 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 bindingfactor 1 (GATA-1), that is critical for normal erythropoiesis, globingene 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
___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
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