Hemoglobinopathies and Porphyrias Flashcards
porphyrins - four atomic rings joined by \_\_ bridges A. sulfide B. chloride C. methene D. pentene
C
product formed in the first reaction of the heme biosynthesis pathway
S-aminolevulinic acid
the enzyme for the first reaction of heme biosynthesis pathway is due to the deficiency of what vitamin?
B6
the enzyme for the first reaction of heme biosynthesis pathway leads to formation of ___
siderosomes
location in the cell for 2nd reaction of heme biosynthesis pathway A. mitochondrion B. vacuole C. cytosol D. nucleus
C
product formed in the second reaction of the heme biosynthesis pathway
porphobilinogen
S-aminolevulinic acid is formed from which 2 reactants?
glycine
succinyl-CoA
the enzyme required to catalyze production of porphobilinogen requires \_\_ A. iron B. zinc C. calcium D. AOTA
B
ALAD Deficient Porphyria is autosomal recessive genetic disorder. ALAD is the enzyme for the 2nd reaction for heme formation. It stands for __
aminolevulinic acid dehydratase
product formed in the third reaction of the heme biosynthesis pathway
hydroxymethylbilane
Which is not an enzyme in the 3rd rxn for heme formation? A. Aminolevilinic dehydratase B. Porphobilinogen deaminase C. Hydroxymethylbilane synthase D. Uroporphyrinogen I synthase
A
Acute intermittent porphyria is caused by defect in gene encoding for: A. Aminolevilinic dehydratase B. Porphobilinogen deaminase C. Hydroxymethylbilane synthase D. Uroporphyrinogen I synthase
B
Most important fate of hydroxymethylbilane A.uroporphyrinogen I B.uroporphyrinogen II C.uroporphyrinogen III D.NOTA
C
Porphyria caused by defect in uroporphyrinogen III synthase
Congenital erythropoietic porphyria
Porphyria caused by defect in urodecarboxylase
Porphyria cutanae tarda
Porphyria cutanae tarda - differentiate type I fr II
Type I - mutations affected only hepatic enzyme
Type II - mutations affecting non-hepatic tissue
IM Prod @ the 5th reaction of heme biosynthesis pathway
Protoporphyrinogen IX
Hereditary coproporphyria is caused by a mutation in this specific gene. Identify the gene, which codes for enzyme @ 5th rxn of heme biosyn pathway
gene coding for coproporphyrinogen-III oxidase
IM prod @ the 6th reaction of heme biosynthesis pathway
Protoporphyrin IX
Variegate coproporphyria is caused by a mutation in this specific gene. Identify the gene, which codes for enzyme @ 6th rxn of heme biosyn pathway
Protoporphyrinogen IX oxidase
Product @ the 7th reaction of heme biosynthesis pathway. How does this come about?
Heme b
Insertion of ferrous ion @ ring system
Erythropoietic coproporphyria is caused by a mutation in this specific gene. Identify the gene, which codes for enzyme @ final rxn of heme biosyn pathway
Gene for ferrochelatase enzyme
Arrange in sequence @ heme biosyn pathway
A.Protoporphyrin IX B.Uroporphyrinogen III C.Protoporphyrinogen IX D.Aminolevulinic acid E.Heme B F.Porphobilinogen G.Hydroxymethylbilane
D.Aminolevulinic acid F.Porphobilinogen G.Hydroxymethylbilane B.Uroporphyrinogen III C.Protoporphyrinogen IX A.Protoporphyrin IX E.Heme B
(1) Three enzymes @ heme biosyn pathway that are highly sensitive to heavy metal poisoning: enumerate
(2) Which among the 3 is most significant?
Ferrochelatase - MOST SIG, CLINICALLY
Aminolevulinic acid synthase
Aminolevulinic acid dehydratase
Among the ff, which is most soluble in urine? (More than 1 answer)
A.Protoporphyrin IX B.Uroporphyrinogen III C.Protoporphyrinogen IX D.Aminolevulinic acid E.Heme B F.Porphobilinogen G.Hydroxymethylbilane
D.Aminolevulinic acid
F.Porphobilinogen
B.Uroporphyrinogen III
Among the ff, which is not seen in urine?
A.Protoporphyrin IX B.Uroporphyrinogen III C.Protoporphyrinogen IX D.Aminolevulinic acid E.Heme B F.Porphobilinogen G.Hydroxymethylbilane
A
Two most common clin manif of porphyria- enumerate
Neurovisceral abnormalities
Cutaneous sensitivity
Two early of porphyria- enumerate
Staining of teeth
Red/port wine color to the urine after exposure to air
Which is false about secondary porphyria?
A.Aminolevulinic acid level increased
B.Porphobilinogen level increased
C.Lead poisoning causes increased coproporphyrinogen, leading to this diseases
B
They remain normal
Porphyrin analysis - enumerate the products & precursors that are part
Aminolevulinic acid Porphobilinogen Uroporphyrinogen III Protoporphyrinogen IX Coproporphyrinogen III
Enumerate & Differentiate the two most common screening tests for urinary Porphobilinogen.
Watson-Schwartz
Hoesch
WS - need to eliminate urobilinogen
H - no need
Explain basis of two most common screening tests for urinary Porphobilinogen
PBG + Erlich’s reagent –> red orange color
Which is measured by Erlich’s test? ( more than 1 answer )
A.Aminolevulinic acid B.Porphobilinogen C.Uroporphyrinogen III D.Protoporphyrinogen IX E.Coproporphyrinogen III
A and B
Porphyrin tests - which is true?
A.zinc protoporphyrins increase in amount when there is much iron
B. Faint blue is positive result in fluorescence
C. Molecular diagnostics - for asymptomatic gene carriers
C
A-Fe insuff dapat
B-Violet,pink,red dapat
Which is false about thalassemia?
A.RBC are hypochromic
B.autosomal dominant disorder
C.thalassemia major resembles Fe def
C
Minor dapat
Most clinically severe alpha thalassemia. Total absence of gamma chain.
Hydrops fetalis
Alpha chain sunthesis at about onethird of beta chain synthesis. Hgb H formed, altering shape of RBC & life span.
Identify alpha thalassemia
Hemoglobin H disease
Which has more alpha gene deletions between the two thalassemias?
A. Alpha thalassemia trait
B. Silent carriers
C. Equal lang sila
A
Differentiate Beta-(+) thalassemia fr Beta-0 thalassemia. Which is more common?
Beta-(+) : chains produced in reduced amount. More common
Beta-0: chains are completely absent
Increase in alpha chains + bone marrow size inc + structural bone abnormalities
Which one? A. Heterozygous Beta-thalassemia B. Homozygous Beta-thalassemia C. BOTA D. NOTA
B
Only one thalassemia gene inherited. Clinically asymptomatic usually.
Which one? A. Heterozygous Beta-thalassemia B. Homozygous Beta-thalassemia C. BOTA D. NOTA
A
Which lab method is used to differentiate thalassemia minor from iron deficiency anemia? A. Isoelectric focusing B. HPLC C. Blood film evaluation D. Serum ferritin
D
Explain solubility test for Hgb
Sickling Hgb @ deoxy state is relatively insoluble and forms ppt when placed & high molarity phosphate buffer
Which is not false (-) for Hgb?
A.anemia
B.recent transfusion
C.hyperlipidemia
C
Which is not false (+) for Hgb? A.erythrocytosis B.recent transfusion C.hyperlipidemia D.hyperglobulinrmia
B
Order of electrophoretic mobility @ cellulose acetate Hgb electrophoresis. Arrange!!!
A. HgbS
B. HgbA
C. HgbC
D. HgbF
C
A
B
D
Which is performed in alkaline setting? A. Cellulose acetate electrophoresis B. Citrate agar electrophoresis C. BOTA D. NOTA
A
Which is performed in acidic setting? A. Cellulose acetate electrophoresis B. Citrate agar electrophoresis C. BOTA D. NOTA
B
Enumerate adult HgB similar in solubility to Hgb A
D I E G O
Which is not a differentiating feature of porphyria cutanae tarda? A.liver damage in patients B.decreased excretion of uroporphyrin C.iron depletion D.NOTA
B
Increased dapat
Which is false? A.HgbC & E: net (+) charge B.HgbA: like HgbS but with (+) charge C.Hgb E: often seen with thalassemia D.NOTA
B
(-) charge dapaf
Which is false?
A. HgbS may manifest as tissue hypoxia
B. All positive cases for HgbS have abnormal blood film
C. HgbS & HgbC: heterozygous - asymptomatic
D. HgbSC: positive solubility test
B
Identify the hemoglobinopathy: glycine substituted by glutamic acid A. HgbA B. HgbC C. HgbD D. HgbE
c
Identify the hemoglobinopathy: no normal beta chain to produce HgbA A. HgbS B. HgbC C. HgbSC D. HgbE
C
Identify the hemoglobinopathy: glutamic acid substituted by lysine A. HgbS B. HgbC C. HgbSC D. HgbE
B
Identify the hemoglobinopathy: glutamic acid substituted by valine A. HgbS B. HgbC C. HgbSC D. HgbE
A
Which is true?
A.Individual Hb chains are under genetic control.
B.Hb synthesis does not occur in reticulocytes.
C.Heme is synthesized in vacuoles of cells.
D.Globin chain is synthesized in mitochondria
A
B - meron
C - mitochondria
D - ribosomes
Differentiate hemoglobinopathies from thalassemias
hemoglobinopathies - fr defects in hemoglobin structure control
thalassemias - fr defects in control of hemoglobin production rate
Not used to treat porphyria A. Avoiding sunlight B. Intravenos hematin C. Reduce heme load by phlebotomy D. Oral alpha-carotene
D
Beta-carotene dapat
Which does not have photosensitivity as symptom? A. Variegate porphyria B. Porphyria cutanae tarda C. Acute intermittent porphyria D. Congenital erythropoietic porphyria
C
NOT hepatic class porphyria
A. Variegate porphyria
B. X-linked sideroblastic anemia
C. Acute intermittent porphyria
D. Congenital erythropoietic porphyra
B
Which enzyme, if with defect, may lead to neurovisceral symptoms? A. Ferrochelatase B. Protoporphyrinogen-IX oxidase C. Uroporphyrinogen III synthase D. NOTA
B
Most common porphyria A. Variegate porphyria B. Porphyria cutanae tarda C. Acute intermittent porphyria D. Congenital erythropoietic porphyria
B
