Porphyria-R - Lab Test Consult
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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
