Organic acidemias

Question 1

Typical presentation of organic acidemia

Answer 1

Vomiting
Failure to Thrive
Developmental delay
Metabolic acidosis
Hyperammonemia

Question 2

Methylmalonic acidemia

• cause
• responsive vs unresponsive

Answer 2

Blocked methylmalonyl-CoA mutase
Can also be caused by cofactor, adenosylcobalamia, defects

B12 responsive and non-responsive form; determine responsiveness clinically

“benign” form with lower level elevations of plasma and urine MMA

Question 3

Methylmalonic acidemia complications

Answer 3

Renal disease
Gout 
Hyperuricemia
Pancreatitis
Metabolic "stroke" with subsequent involuntary movement may occur
Optic atrophy or retinitis
Prolonged QT

Question 4

Propionic acidemia

Answer 4

Propionyl-CoA carboxylase (PCC) deficiency

deficiency can also be due to biotin deficiency

Question 5

Propionic acidemia complications

Answer 5

Recurrent pancreatitis
Cardiomyopathy common, common cause of death
Prolonged QT
Optic atrophy and retinitis
Metabolic stroke
**these symptoms are due to secondary respiratory chain defects

Question 6

Acute management of organic acidemias

Answer 6

NPO – cut protein dose
Reversal of catabolism
Correction by bicarbonate replacement
Detoxofication with levocarnitine or hemodialysis

Question 7

Long- term treatment of MMA

Answer 7

RESTRICT SUBSTRATE

• restrict amino acids, low protein diet
• antibiotics to reduce gut bacteria’s production of propionic acid

PROVIDE COFACTOR: HydroxyB12

ALT. ROUTE OF ELIMINATION: Carnitine

OTHER: Bicitra for acid-base stabilization

Question 8

Long- term treatment of PA

Answer 8

RESTRICT SUBSTRATE

• restrict amino acids, low protein diet
• antibiotics to reduce gut bacteria’s production of propionic acid

PROVIDE COFACTOR: Biotin

ALT. ROUTE OF ELIMINATION: Carnitine

OTHER: Bicitra for acid-base stabilization

Question 9

Cobalamin C disease

Answer 9

Cofactor for both MMA and methionine synthase, so can cause both methylmalonic aciduria and homocysteinuria
Can also cause:
- mental retardation
- seizures
- nystagmus (eye problems)
- cardiac abnormalities
- abnormal dentition

Question 10

Isovaleric acidemia

Answer 10

Deficiency of isovaleryl CoA Dehydrogenase

Inability to fully metabolize leucine

Accumulation of isovaleric acid, isovalerylglycine, isovalerylcarnitine, 3-hydroxyisovaleric

Question 11

Clinical Presentation of isovaleric acidemia

Answer 11

ACUTE FORM:
- neonatal period with vomiting, lethargy, metabolic acidosis, hyperammonemia, ketonuria, odor, pancytopenia

CHRONIC INTERMITTENT FORM:
- first decompensation follows stressor

Asymptomatic variant

Question 12

Treatment of isovaleric acidemia

Answer 12

RESTRICT SUBSTRATE - low protein diet, restrict leucine

ALT ROUTES OF ELIMINATION

• carnitine
• glycine (has low glycine because acid formation captures glycine. Other classical acidemias have high glycine)

OTHER: Bicitra for acid-base stabilization

Question 13

Isovaleric acidemia

• genetics
• diagnosis
• prognosis

Answer 13

AR

assay isovaleryl CoA DH in amniocytes, or quantify isovalerylglycine in amniotic fluid

PROGNOSIS: usually very good with normal neurologic outcome

Question 14

3-MCC (3-methylcrotonyl CoA Carboxylase Deficiency)

• symptoms
• treatment

Answer 14

Leucine catabolic pathway

• maybe most common organic acidemia
• -> most asymptomatic

SYMPTOMS:

• ketoacidosis
• vomiting
• hypoglycemia

TREATMENT:
- protein restriction, biotin, carnitine