W01_01 Intro to metabolic disease Flashcards Preview

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Flashcards in W01_01 Intro to metabolic disease Deck (23)
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1
Q

what is phenylketonuria?

A

autosomal recessive due to mutations in the phenylalanine hydroxylase (PAH) gene. the result is higher phenylalanine (toxic) and decreased tyrosine.

2
Q

what do increased phenylalanine levels cause?

A

competes with brain’s amino acid transporter, so there’s lower concentration of other AAs

3
Q

low tyrosine and low tryptophan leads to low levels of what?

A

dopamine and serotonin

4
Q

what’s the final result of PKU in the brain?

A

defective myelination, cognitive problems, seizures, small brain

5
Q

how can PKU cause fair skin/hair?

A

low tyrosine = low melanin

6
Q

what’s the dietary treatment for PKU?

A

reduce intake of phenylalanine with special diets

reduce protein intake

7
Q

what’s the medical treatment for PKU?

A

1) large neutral amino acid therapy, to compete for phenylalanine and prevent its uptake;
2) sapropterin BH4: PAH enzyme enhancer;
3) phenylalanine lyase (PAL) alternative metabolism of phenylalanine to cinnamic acid

8
Q

which molecule is a common congregation of the protein/carb/lipid metabolic pathways?

A

acetyl-CoA

9
Q

what’s glycogen storage disease type 1?

A

glucose-6-phosphatase doesn’t work, so can’t get glucose from glycogen

10
Q

what happens if you give a GSD1 patient glucagon?

A

they’ll produce G6P, but instead of getting glucose, they’ll make lactic acid and triglycerides and uric acid

11
Q

what are clinical features of GSD1?

A

massive hepatomegaly;
hypoglycemia;
high triglycerides;
high uric acid

12
Q

what’s the management of GSD1?

A

take cornstarch throughout the day to replenish the glucose supplies;
treat other symptoms of triglycerides and uric acid

13
Q

note: there are emerging neonatal gene therapies for GSD1, and hepatocyte transplantation techniques

A

ok

14
Q

what are clinical features of organelle diseases?

A

correlation to the organs where complex molecules accumulate; OR
correlation to specific organs where the organelles are preferentially utilized (e.g. mitochondria in the muscles, brain, heart)

15
Q

what is lysosomal storage disease?

A

a deficiency of one or more of the many lysosomal hydrolases

16
Q

what are the 3 big mucopolysaccharides we discussed in class?

A
heparan sulfate (accumulates in brain);
dermatan sulfate (accumulates in brain);
keratan sulfate (accumulates in bone)
17
Q

how to molecularly diagnose MPS?

A

thin-layer chromatography

18
Q

clinical features of hurler syndrome? (MPS I)

A

chronic runny nose + recurrent otitis media;
umbilical and inguinal hernias;
coarse facies;
corneal clouding;
large liver+spleen;
developmental slowiing by year 2
increase in dermatan, keratan, heparan sulfates

19
Q

what causes MPS I?

A

defect in iduronidase enzyme

20
Q

what’s the treatment for MPS I?

A

enzyme replacement therapy (aldurazyme);
bone marrow transplant;
symptomatic management

21
Q

what has aldurazyme shown as treatment results?

A

better joint RoM;
smaller liver;
improvements in cardiac, pulmonary function

22
Q

limitations of ERT?

A

allergic reactions;
can’t cross BBB;
expensive

23
Q

note: bone marrow transplantation can fix brain issues in LSD if given early enough (< 2 years, and IQ > 70%)

A

ok

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