Lecture 26-Biochemical Metabolism

Question 1

What are the symptoms of a UCD? What are the labs that show each of these?

Answer 1

• hyperammonemia: high ammonia and glutamine
• vomiting
• lethargy/coma: low ketones, proteins, reducing substrates, blood BUN, arginine
• respiratory alkalosis

Question 2

Refresher: how do you treat UCDs?

Answer 2

• scavengers: sodium benzoate (glycine), phenylacetate: (glutamine)
• reduce protein intake
• reduce protein breakdown: insulin temporarily, high carb diet
• dialysis
• arginine supplementation

Question 3

MSUD is a defect of what enzyme?

Answer 3

• branched chain ketoacid DH

Question 4

MSUD results in accumulation of what?

Answer 4

• 2-oxo (keto)acids

Question 5

What is a clinical way to determine MSUD disease? What are the labs results you can use to determine if it’s MSUD (4)?

Answer 5

• Clinical: intense smell of urine

Labs:

• characteristic plasma aa abnormalities
• increase in BCAA
• disturbed BCAA ratio
• lots of ketones

Question 6

treatment for MSUD? (4)

Answer 6

• dialysis
• high energy, low protein TPN/enteral feeds (MSUD specific)
• leu restriction
• thiamine supplementation

Question 7

What is the primary toxic aa?

Answer 7

• leucine

Question 8

what are the prognoses for MSUD? (4)

Answer 8

• decompensations
• disability
• pancreatitis
• epidermolysis

Question 9

MMA/PA stand for _____

Answer 9

• methyl-malonyl CoA mutase

- proprionyl CoA carboxylase

Question 10

MMA and PA do what?

Answer 10

• sequential steps in isoleucine and valine catabolism

- needed for odd chain FA breakdown

Question 11

What are the symptoms of MMA/PA? (6)

Answer 11

• ACIDEMIA
• respiratory distress
• poor feeding
• abnormal muscle tone
• vomiting
• seizures
• toxic encephalopathy

Question 12

What is diagnostic of MMA/PA

Answer 12

• methylcitric acid

- 3OH propionate

Question 13

What accumulates in both MMA and PA diseases? Why is this bad?

Answer 13

• proprionic acid

- converted into many UOA biproducts

Question 14

What do the labs on MMA/PA show?

Answer 14

• metabolic acidosis with increased anion gap
• ketosis
• hyperammonemia
• hypoglycemia
• hyperglycinemia
• neutropenia
• elevated amylase/lipase

Question 15

How do you treat MMA/PA? (8)

Answer 15

• **rehydration
• **promote anabolism
• **VOMIT restriction (aa)
• **carnitine supplementation
• biotin/cobalamin supplementation
• metronidazole
• get rid of excess precursors
• dialysis

Question 16

How do patients respond to treatment of MMA/PA?

Answer 16

• well if caught early and vitamin responsive, otherwise not well

Question 17

Isovaleric acidemia is the result of a mutation in what? What kind of protein is this?

Answer 17

• isovaleryl-CoA DH

- mitochondrial flavoprotein in ETC

Question 18

How do IVA patients generally present?

Answer 18

• Similar to MMA/PA but milder

- smell like sweaty gym socks

Question 19

PKU is a deficiency in what enzyme?

Answer 19

• F-hydroxylase deficiency

Question 20

PKU results in what symptoms? (3)

Answer 20

• MR
• autistic behavior
• seizures

Question 21

How do you treat IVA?

Answer 21

• rehydrate
• promote anabolism
• give lots of gly and carnitine as a way to get rid of the Isovaleryl CoA
• restrict leucine

Question 22

What is very effective at preventing further decompensation in IVA patients?

Answer 22

• gly

- carnitine

Question 23

In the lecture, PKU was mentioned to emphasize _____

Answer 23

the importance of screening

Question 24

What is PKU inheritance?

Answer 24

• AR

Question 25

New population to worry about with PKU?

Answer 25

• moms who are restricting PKU