B3-092 Porphyria Flashcards
1
Q
porphyria is caused by
A
partial deficiency of heme biosynthesis enzymes
2
Q
porphyria results in the accumulation of _____________ in tissues
A
heme precursors
3
Q
all autosomal dominant porphyrias have
A
low clinical penetrance
4
Q
Heme is necessary for [3 functions]
A
oxygen binding
oxygen metabolism
electron transfer
5
Q
most heme is synthesized by _________ cells in bone marrow and ____________ in the liver
A
erythroid; hepatocytes
6
Q
4 pyrrole rings linked by methenyl bridges
A
ferrous iron (Fe2+) and protoporphyrin IX
7
Q
porphyrias can be classified into two main groups based on predominant clinical manifestations
A
causing acute neurovisceral attacks
porphyrias causing chronic cutaneous photosensitivity
8
Q
ALA dehydratase deficiency affects which enzyme?
A
ALAD
9
Q
Does ALA dehydratase deficiency have neurovisceral or skin manifestations?
A
neurovisceral
10
Q
inheritance pattern: ALA dehydratase deficiency
A
autosomal recessive
11
Q
Acute intermittent porphyria affects which enzyme?
A
HMBS
12
Q
does Acute intermittent porphyria cause neurovisceral or skin manifestations?
A
neurovisceral
13
Q
inheritance pattern: Acute intermittent porphyria
A
autosomal dominant
14
Q
hereditary coproporphyria affects which enzyme?
A
CPO
15
Q
does hereditary coproporphyria cause neurovisceral or skin manifestations?
A
both
16
Q
inheritance pattern: hereditary coproporphyria
A
autosomal dominant
17
Q
Variegate affects which enzyme?
A
PPOX
18
Q
does variegate cause neurovisceral or skin manifestations?
A
both
19
Q
inheritance pattern: variegate
A
autosomal dominant
20
Q
congenital erythropoietic porphyria affects which enzyme?
A
UROS
21
Q
does congenital erythropoietic porphyria cause neurovisceral or skin manifestations?
A
skin
22
Q
inheritance pattern: congenital erythropoietic porphyria
A
autosomal recessive
23
Q
porphyria cutanea tarda affects which enzyme?
A
UROD
24
Q
does porphyria cutanea tarda exhibit neurovisceral or skin manifestations?
A
skin
25
inheritance pattern: porphyria cutanea tarda
complex
26
which enzyme does erythropoietic protoporphyria affect?
FECH
27
does erythropoietic protoporphyria cause neurovisceral or skin manifestations?
skin
28
inheritance pattern: erythropoietic protoporphyria
autosomal dominant
29
enzyme defects up to _________ cause acute neurologic porphyria
HMBS
30
enzyme defects up to HMBS cause
acute neurologic porphyria
31
enzyme defects after HMBS are ______________ and cause cutaneous porphyria
less soluble
32
enzyme defects after HMBS are less soluble and cause
cutaneous porphyria
33
VP and HCP ____________ PBG production
increase
34
increased PBG production interferes with _____________ causing neurovisceral attacks
GABA signaling
35
increased PBG production interferes with GABA signaling causing
neurovisceral attacks
36
enzyme deficiency, combined with _________________ causes an imbalance in the heme pathway
environmental or physiologic trigger
37
overproduction of porphyrins and porphyrin precursors into blood causes
skin lesions
38
overproduction of porphyrins and porphyrin precursors into the liver cause
acute neurologic symptoms
39
overproduction of porphyrins and porphyrin precursors into bone marrow cause
acute neurologic symptoms
40
common triggers that induce ALA synthase
alcohol use
smoking
medications
hormone replacement
sunlight exposure
stress
dieting and fasting
41
symptoms of cutaneous porphyrias
oversensitivity to sunlight
blisters on sun exposed skin
skin fragility
scarring
hyper or hypo pigmentation
hypertrichosis/alopecia
urticaria
42
porphyrins deposited in skin absorb energy in the visible light spectrum causing
oxidative damage
43
porphyrins deposited in skin absorb energy in the _____________ causing oxidative damage
visible light spectrum
44
most common porphyria
porphyria cutanea tarda
45
porphyria cutanea tarda onsets in which stage of life?
adulthood
46
porphyria cutanea tarda is more common in women or men?
men
47
______% of porphyria cutanea tarda causes are acquired
75
48
causes of acquired porphyria cutanea tarda
hep C
hemochromatosis
alcohol abuse
smoking
estrogen rx
polychlorinated cyclic hydrocarbon exposure
49
in porphyria cutanea tarda ________ accumulates in skin
uroporphyrin
50
porphyria cutanea tarda is symptomatic when enzyme is
<20% of normal
51
porphyria cutanea tarda causes the inability to convert uroporphyrinogen to
coproporphyrinogen
52
porphyria cutanea tarda causes the inability to convert _______________ to coproporphyrinogen
uroporphyrinogen
53
in porphyria cutanea tarda, LFTs are
abnormal
54
porphyrins in the liver down regulate
hepcidin
55
down regulation of hepcidin causes
iron overload and formation of ROS
56
treatment of porphyria cutanea tarda
avoid sunlight
discontinue. risk factors
treat comorbid conditions
phlebotomy
57
congenital erythropoietic porphyria is caused by a deficiency in
uroporphyrinogen III synthase
58
erythropoietic protoporphyria is caused by a deficiency of
ferrochelatase
59
most common early childhood porphyria
erythropoietic protoporphyria
60
causes acute photosensitivity without skin fragility and blisterin
erythropoietic protoporphyria
61
erythropoietic protoporphyria is caused by a deficiency of
ferrochelatase
62
erythropoietic protoporphyria increases the risk of
hemolytic anemia
gallstones
liver disease (may require transplant)
63
erythropoietic protoporphyria treatment
avoid sunlight
melanocyte stimulating hormone to darken skin and reduce photosensitivity
narrowband UVB to darken skin
cholestyramine to absorb protoporphyrin
stem cell transplant
**liver transplant if liver failure
64
in erythropoietic protoporphyria, excess protoporphyrin accumulates in
RBCs
diffuses into plasma, enters skin, cleared by liver and secreted into bil
65
associated with vampire folklore
congenital erythropoietic porphyria
66
onset soon after birth
congenital erythropoietic porphyria
67
severe photosensitivity with scarring, erythrodontia, hemolytic anemia, and gallstone
congenital erythropoietic porphyria
68
porphyrin laden erythrocytes in congenital erythropoietic porphyria cause
hemolysis, splenomegaly, gallstones
photolysis in dermal capillaries
69
caused by enzyme defect in bone marrow erythroid cells
congenital erythropoietic porphyria
70
congenital erythropoietic porphyria treatment
avoid sunlight
transfusion for anemia
stem cell transplant
71
chronic cutaneous manifestations may lead to misdiagnosis
variegate porphyria
72
chronic cutaneous manifestations with abdominal pain, neuropathy, and psychiatric
variegate porphyria
73
rarest forms of porphyria
hereditary coproporphyria
74
usually provoked by cholestasis from some other cause
hereditary coproporphyria
75
increased coproporphyria in urine and feces
hereditary coproporphyria
**similar to VP
76
coproporphyrin III:I ratio of 10-20 with no increase in protoporphyrin
hereditary coproporphyria
77
symptoms of acute neurologic porphyrias
severe abdominal pain
psychiatric distress
hypertensions, tachycardia
seizures
parasthesia
fever
weakness progressing to paralysis
78
acute neurologic porphyrias can be provoked by
barbituates
sulfonamide antibiotics
anticonvulsants
antihistamines
chemicals
smoking
alcohol
caloric restriction
79
in ALAD and AIP, tetrapyrrole intermediates
do not accumulate
80
ALAD and AIP do not cause
photosensitivity
81
VP and HCP increase ___________ & do cause photosensitivity
tetrapyrrole
82
VP and HCP increase tetrapyrrole and cause
photosensitivity
83
onset between 15-35 years
acute porphyria
**rare before puberty
84
acute porphyria is more common in women or men?
women
85
characterized by acute neurovisceral attacks
acute porphyria
86
recurrence of acute porphyria may be related to the __________________ in women
menstrual cycle
87
acute porphyria is difficult to diagnose because
symptoms are non specific and variable
family history often missing or incomplete
88
PBG is almost always increased in
AIP, VP, and HCP
89
most common acute porphyria
AIP
90
higher incidence in northern europe
AIP
91
sequence of symptoms, AIP
abdominal pain --> psychiatric --> peripheral neuropathy
92
GI symptoms of AIP
constipation
colicky abdominal pain
vomiting
diarrhea
93
psychiatric symptoms of AIP
psychotic episodes
depression
anxiety
94
in AIP, excess PBG and ALA are
neurotoxic
95
ALA interferes with
GABA signaling
96
heme deficiency inhibits cytochromes and causes
neurodegeneration
97
heme deficiency decreases hepatic tryptophan pyrrolase activity resulting in
increased serotonin and cognitive changes
98
port wine urine
AIP
99
in AIP, excess porphobilinogen and aminolevulinic acid are excreted in
urine
100
extremely rare acute neurologic porphyria
ALAD
101
only acute porphyria to begin in childhood
ALAD
102
ALAD has _________ levels of urine porphobilinogen
normal
103
ALAD has ______________ aminolevuliniv acid
significantly elevated
**rule out lead poisoning
104
treatment: acute porphyrias
treat symptoms and try to correct heme pathway deficiency
105
therapeutic options for acute porphyrias
remove exacerbating factors
IV fluid with dextrose
opiate pain control
nausea control
hematin IV therapy
106
panhematin is infused IV and taken up by
hepatocytes --> enters heme pool
107
panhematin inhibits synthesis of
ALA synthase
**rate limiting enzyme of heme pathway
108
ultimately, panhematin reduces production of
porphyrin precursors
109
RNA interference drug targeting Aminolevulinic acid synthase
givlaari
110
alternative to hemin infusions for patients with frequent acute porphyria attacks
givlaari
111
best initial test to diagnose porphyrias
urine porphyring analysis + porphobilinogen
**erythrocyte protoporphyrin if EPP suspected
112
Confirmatory PCT testing:
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay:yes
Urine elevations: uroheptacarboxyl
Feces elevations: isocopro heptacarboxyl
Erythrocyte elevations: none
plasma elevations: uroheptacarboxyl
113
confirmatory EPP testing:
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: no
Urine elevations: no
Feces elevations: proto
Erythrocyte elevations: proto
plasma elevations: proto
114
confirmatory CEP testing:
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: yes
Urine elevations: Uro I, Copro I
Feces elevations: Copro I
Erythrocyte elevations: Uro I, Copro I
plasma elevations: Uro I, Copro I
115
confirmatory AIP testing:
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: yes
Urine elevations: ALA, PBG, Uro, Copro
Feces elevations: Uro
Erythrocyte elevations: no
plasma elevations: Uro
116
confirmatory VP testing
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: no
Urine elevations: ALA, PBG, Copro
Feces elevations: proto>copro, copro III/I
Erythrocyte elevations: no
plasma elevations: copro, proto
117
confirmatory HCP testing
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: no
Urine elevations: ALA & PBG, copro
Feces elevations: copro III/I
Erythrocyte elevations: no
plasma elevations: copro
118
confirmatory testing ALAD
Enzyme Assay:
Urine elevations:
Feces elevations:
Erythrocyte elevations:
plasma elevations:
Enzyme Assay: yes
Urine elevations: ALA copro
Feces elevations: no
Erythrocyte elevations: zinc
plasma elevations: n/a
119
only order __________ after biochemical diagnosis has been made to confirm diagnosis
molecular test
120
molecular testing for at risk family members
test for mutation identified in family
counsel to avoid exacerbating factors
121
heme pathway
122
3 most common porphyrias in US
Acute intermittent
erythropoietic protop.
cutanea tarda
123
most common porphyria in US
cutanea tarda
124
second most common porphyria in US
AIP
125
third most common porphyria in US
erythropoietic protoporhyria
126
presents with acutely painful skin lesions
erythropoietic protoporphyria
127
presents with acute neurovisceral symptoms
AIP
128
presents with chronic blistering skin lesions
porphyria cutanea tarda
129
the intermittent symptoms of porphyrias is due to
partial deficiencies in the heme pathway
130
cutanea tarda is caused by
uroporphyrinogen decarboxylase deficiency
131
erythropoietic protoporphyria is caused by
ferrochelatase deficiency
132
congenital erythropoietic porphyria is caused by
UROS
133
congenital erythropoietic porphyria is inherited in an
autosomal recessive pattern
