Organic Acidemias Flashcards
What are organic acids?
Deaminated remains of amino acids (-NH3)
What happens if there is defective degradation of organic acids?
accumulation of organic acids leads to:
- Metabolic acidosis WITH elevated anion gap
- Hyperammonemia
- Hypoglycemia
How are organic acidemias inherited?
Autosomal recessive
What are 4 general features seen in organic acidemias in the newborn period?
- Poor feeding
- Lethargy
- Vomiting
- Tachypnea
Generally seen in the first few days after birth
How do you diagnose organic acidemias? What investigations should be done?
- Newborn screening
- Plasma amino acid analysis
- Urine organic acid analysis
What are the general treatment strategies used to tx organic acidemias?
- Stop ALL protein intake
- Give high dose carnitine
- Promote anabolic state with IV glucose
- IV lipid emulsions and sometimes insulin or bicarbonate
- May need hemodialysis
- Restrict the offending amino acids
What enzyme is deficient in propionic acidemia?
Defect in Propionyl CoA carboxylase
Defect in propionyl CoA carboxylase leads to abnormal metabolism of what amino acids?
- Isoleucine
- Valine
- Methionine
- Threonine
Name 5 features of propionyl acidemia in the neonatal period
- Ketosis
- High ammonia
- Pancreatitis
- Pancytopenia
- Intellectual disability from acute episodes
What 2 late onset complications can be seen with uncontrolled propionyl acidemia?
- Cardiomyopathy
2. Cardiac dysrythmia
What will urine organic acid analysis show in propionyl acidemia?
High levels of 3-OH proprionic acid, and methylcitrate
What will NBS show in propionic acidemia?
C3 acylcarnitine
What amino acids will be high in serum in propionic acidemia?
Glycine
What enzyme is deficient in methylmalonic acidemia?
Methylmalonyl CoA mutase (step after the one involved in propionic acidemia)
How does methylmalonic acidemia present in the neonatal period?
- Ketosis
- High ammonia
- Pancreatitis
- Pancytopenia
- ID from acute episodes
What long term sequelae is unique to methylmalonic acidemia?
Late onset renal disease
What will urine organic acid analysis show in methylmalonic acidemia?
Methylmalonic acid and methylcitrate
What will NBS show in methylmalonic acidemia?
C3 acylcarnitine
What will plasma amino acid analysis show in methylmalonic acidemia?
Glycine and alanine
What is type 1 glutaric acidemia caused by?
Defect in glutaryl CoA dehydrogenase
What amino acids does glutaryl CoA dehydrogenase break down?
tryptophan, hydroxylysine and lysine
Name 2 ways glutaric acidemia may present
- Can have a classic neonatal hyperammonia, metabolic acidosis, ketosis presentation but not always!
- 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
How should glutaric acidemia be tx acutely?
Long term?
Acutely: IVD10, carnitine
Chronic: Carnitine, diet modifications
What will urine organic acids show in glutaric acidemia?
High glutaric acid, and 3-OH glutaric acid
What will NBS show in individuals with glutaric acidemia?
C5 dicarboxylic acylcarnitine
