Organic Acidemias

Question 1

What are organic acids?

Answer 1

Deaminated remains of amino acids (-NH3)

Question 2

What happens if there is defective degradation of organic acids?

Answer 2

accumulation of organic acids leads to:

1. Metabolic acidosis WITH elevated anion gap
2. Hyperammonemia
3. Hypoglycemia

Question 3

How are organic acidemias inherited?

Answer 3

Autosomal recessive

Question 4

What are 4 general features seen in organic acidemias in the newborn period?

Answer 4

1. Poor feeding
2. Lethargy
3. Vomiting
4. Tachypnea
   Generally seen in the first few days after birth

Question 5

How do you diagnose organic acidemias? What investigations should be done?

Answer 5

1. Newborn screening
2. Plasma amino acid analysis
3. Urine organic acid analysis

Question 6

What are the general treatment strategies used to tx organic acidemias?

Answer 6

1. Stop ALL protein intake
2. Give high dose carnitine
3. Promote anabolic state with IV glucose
4. IV lipid emulsions and sometimes insulin or bicarbonate
5. May need hemodialysis
6. Restrict the offending amino acids

Question 7

What enzyme is deficient in propionic acidemia?

Answer 7

Defect in Propionyl CoA carboxylase

Question 8

Defect in propionyl CoA carboxylase leads to abnormal metabolism of what amino acids?

Answer 8

1. Isoleucine
2. Valine
3. Methionine
4. Threonine

Question 9

Name 5 features of propionyl acidemia in the neonatal period

Answer 9

1. Ketosis
2. High ammonia
3. Pancreatitis
4. Pancytopenia
5. Intellectual disability from acute episodes

Question 10

What 2 late onset complications can be seen with uncontrolled propionyl acidemia?

Answer 10

1. Cardiomyopathy

2. Cardiac dysrythmia

Question 11

What will urine organic acid analysis show in propionyl acidemia?

Answer 11

High levels of 3-OH proprionic acid, and methylcitrate

Question 12

What will NBS show in propionic acidemia?

Answer 12

C3 acylcarnitine

Question 13

What amino acids will be high in serum in propionic acidemia?

Answer 13

Glycine

Question 14

What enzyme is deficient in methylmalonic acidemia?

Answer 14

Methylmalonyl CoA mutase (step after the one involved in propionic acidemia)

Question 15

How does methylmalonic acidemia present in the neonatal period?

Answer 15

1. Ketosis
2. High ammonia
3. Pancreatitis
4. Pancytopenia
5. ID from acute episodes

Question 16

What long term sequelae is unique to methylmalonic acidemia?

Answer 16

Late onset renal disease

Question 17

What will urine organic acid analysis show in methylmalonic acidemia?

Answer 17

Methylmalonic acid and methylcitrate

Question 18

What will NBS show in methylmalonic acidemia?

Answer 18

C3 acylcarnitine

Question 19

What will plasma amino acid analysis show in methylmalonic acidemia?

Answer 19

Glycine and alanine

Question 20

What is type 1 glutaric acidemia caused by?

Answer 20

Defect in glutaryl CoA dehydrogenase

Question 21

What amino acids does glutaryl CoA dehydrogenase break down?

Answer 21

tryptophan, hydroxylysine and lysine

Question 22

Name 2 ways glutaric acidemia may present

Answer 22

1. Can have a classic neonatal hyperammonia, metabolic acidosis, ketosis presentation but not always!
2. Can also present with macrocephaly and are well UNTIL a metabolic crisis, can have permanent damage of especially basal ganglia areas (movement d/o) after fever

Question 23

How should glutaric acidemia be tx acutely?

Long term?

Answer 23

Acutely: IVD10, carnitine

Chronic: Carnitine, diet modifications

Question 24

What will urine organic acids show in glutaric acidemia?

Answer 24

High glutaric acid, and 3-OH glutaric acid

Question 25

What will NBS show in individuals with glutaric acidemia?

Answer 25

C5 dicarboxylic acylcarnitine