you would like to obtain additional data to make a firm diagnosis for two patien
ID: 176521 • Letter: Y
Question
you would like to obtain additional data to make a firm diagnosis for two patients so that you can come up with some possible treatments for your patients. for each patient answer questions about what additional data would be useful and why. be specific!!
1. patient pedigree constructed from her family history: what types of info will the pedigree for this patient give you?
2. DNA sequences of specific genes:
a - which specific genes will you sequence and why? (assume that as a control, you also sequence non-affected relatives of the patient)
b - if there are mutations in the coding region of the genes you sequence, what will that tell you?
c - if there are mutations in the non-coding regions, what will that tell you?
3. full genome sequence of patient: what potentially useful info will this give you?
4. human cancer database: what potentially useful info will this give you?
These are data that I have and conclusions that I have for each patient so far.
test
average
A
B
glucose
70-100 mg/dL
35 mg/dL
45 mg/dL
lactic acid
5-10 mmol/dL
20 mmol/dL
15 mmol/dL
blood pH
7.3-7.4
7.2
7.25
SpO2
95-100%
95%
98%
pyruvate
35-50 mg/dL
28 mg/dL
30 mg/dL
fructose-2-6-bisphosphate
10-20 mg/dL
15 mg/dL
16 mg/dL
-> both patient A and B are hypoglycemic because of low glucose. so anaerobic break down of glucose to generate energy in muscles provide higher lactate level with low blood pH. the increased lactate concentration will decrease pyruvate and fructose-2-6-bisphosphate.
enzyme
kinetic parameter
average
A
B
glucose transporter-1 (GLUT-1)
Vmax(f)
Km glucose
0.01-0.02
0.09-0.10
0.08
0.09
0.02
0.10
hexokinase (HK)
Vmax (f)
Km glucose
0.05-0.07
0.10-0.30
0.50
0.18
0.09
0.12
phosphofructose kinase (PFK)
Vmax (f)
Km F6P
Km ATP
0.02-0.05
0.50-0.75
0.45-0.65
0.27
0.40
0.55
0.05
0.55
0.55
triose phosphate isomerare (TPI)
Vmax (f)
Km DHAP
0.50-0.80
1.0-3.0
0.58
1.9
0.70
2.5
glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
Vmax (f)
Km GAP
Km NAD+
0.90-1.20
0.20-0.50
0.09-0.20
1.00
0.29
0.10
1.10
0.25
0.09
pyruvate kinase (PK)
Vmax (f)
Km PEP
3.0-5.0
0.30-0.60
13.8
0.40
5.0
0.3
lactate dehydrogenase
Vmax (f)
Km Pyr
8.0-12.0
0.20-0.50
21.8
0.45
13.0
0.20
-> patient A: Km of GLUT-1 is comparable but consistently rate of reaction is fast. has low affinity for glucose as HK has higher Km, but it makes up with much high Vmax. glycolysis occuring at smooth rate (GAPDH). pyruvate gets reduced to lactate under anaerobic condition by LDH action (LDH Vmax is very high).
-> patient B: everything is mostly normal, but the reactions are much slower compared to patient A and normal average data. so the body may not be able to cope up with glucose demand if B moves a lot or exercise a lot.
enzyme
regulator (activator or inhibitor)
average
A
B
hexokinase (HK)
G6P
0.01-0.03
0.02
0.02
phosphofructose kinase (PFK)
ATP
F2, 6BP
1.50-3.00
0.01-0.03
1.75
0.02
8.00
0.001
pyruvate kinase (PK)
ATP
2.00-4.50
2.05
2.50
-> patient A: every criteria falls under the normal healthy average range.
-> patient B: high PFK, may be due to high rate of glycolysis in a cancer cells
enzyme
relative abundance
average
A
B
GLUT-1
mRNA
protein
500-1000
1.0-2.0
2000
5
550
1.5
hexokinase (HK)
mRNA
protein
200-500
0.5-2.0
1400
3.5
220
0.4
phosphofructose kinase (PFK)
mRNA
protein
300-750
2.0-5.0
6000
20.0
550
2.5
triose phosphate isomerase (TPI)
mRNA
protein
50-75
0.5-0.7
55
0.45
60
0.55
glyceraldehyde 3-phosphate dehy. (GAPDH)
mRNA
protein
550-1000
1.0-2.0
520
0.9
600
1.1
pyruvate kinase (PK)
mRNA
protein
250-550
2.0-5.0
1500
12
300
2.4
lactate dehydrogenase (LDH)
mRNA
protein
50-75
0.1-0.3
200
0.6
60
0.1
-> patient A: high lucose uptake because GLUT-1 is high. HK high because glucose is most important substrate of HK and patient has high glucose uptake. high PFK leads to faster metabolism which is not good. high LDH means blood flow deficiency, cerebrovascular accident such as stroke, heart attack or some type of cancer. high PK means problems with red blood cells.
-> patient B: low glucose uptake cmpared to patient A, but falls into normal range. HKf alls into normal because glucose uptake is normal. PFK is also nomral, so matabolism should be normal.
test
average
A
B
glucose
70-100 mg/dL
35 mg/dL
45 mg/dL
lactic acid
5-10 mmol/dL
20 mmol/dL
15 mmol/dL
blood pH
7.3-7.4
7.2
7.25
SpO2
95-100%
95%
98%
pyruvate
35-50 mg/dL
28 mg/dL
30 mg/dL
fructose-2-6-bisphosphate
10-20 mg/dL
15 mg/dL
16 mg/dL
Explanation / Answer
1). Genetic counselling is referred to the information given to the person or a couple about their genetic makeup. On the basis of observation about the individual’s family chart, that is pedigree and genetic screening tests the counsellor determines the genetic makeup. So, the genetic counsellor can explain the chance of getting the disease to their progeny and how to take care of their progeny, etc.
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