Organic Acidemias Flashcards
A 3-day-old male presents with lethargy, poor feeding, and vomiting. Physical examination reveals hypotonia and hepatomegaly. Laboratory studies show a high anion gap metabolic acidosis, hyperammonemia, ketonuria, and elevated methylmalonic acid levels in the urine. Which of the following is the most likely underlying defect?
A) Deficiency of carbamoyl phosphate synthetase I
B) Deficiency of propionyl-CoA carboxylase
C) Deficiency of methylmalonyl-CoA mutase
D) Deficiency of glucose-6-phosphatase
E) Deficiency of pyruvate dehydrogenase
Answer: Deficiency of methylmalonyl-CoA mutase
Explanation: Methylmalonic acidemia is caused by a deficiency of methylmalonyl-CoA mutase or vitamin B12, leading to impaired conversion of methylmalonyl-CoA to succinyl-CoA. This results in the accumulation of methylmalonic acid and propionic acid, leading to metabolic acidosis, hyperammonemia, and ketonuria. The condition typically presents in the neonatal period with poor feeding, vomiting, lethargy, and hypotonia. Laboratory findings confirm elevated methylmalonic acid levels in the urine and serum.
Incorrect Answers:
A) Carbamoyl phosphate synthetase I deficiency causes urea cycle defects, leading to hyperammonemia without acidosis or methylmalonic acid elevation.
B) Propionyl-CoA carboxylase deficiency causes propionic acidemia, which presents similarly but without methylmalonic acid elevation.
D) Glucose-6-phosphatase deficiency (Von Gierke disease) results in severe fasting hypoglycemia, hepatomegaly, and lactic acidosis, not high anion gap metabolic acidosis or hyperammonemia.
E) Pyruvate dehydrogenase deficiency leads to lactic acidosis and neurologic symptoms without methylmalonic acid or hyperammonemia.
What are the two main types of Organic Acidemias?
Propionic Acidemia and Methylmalonic Acidemia
Why does high ion gap metabolic acidosis as well as elevated ammonia occur with organic academia?
- The accumulation of organic acids will inhibit gluconeogenesis, decreasing fasting blood glucose levels, and elevate ketoacidosis, promoting a high anion gap metabolic acidosis.
- These acids also inhibit the urea cycle, and cause hyperammonemia.
What is the genetic inheritance pattern of Organic Acidemias?
Autosomal recessive
When do symptoms of Organic Acidemia manifest?
during infancy.
poor feeding, vomiting, hypotonia, high anion gap metabolic acidosis, hepatomegaly, seizures.
What enzyme is deficient in Propionic Acidemia?
Deficiency of propionyl-CoA carboxylase
increased propionyl-CoA.
decreased methylmalonic acid.
What enzyme is deficient in Methylmalonic Acidemia?
Deficiency of methylmalonyl-CoA mutase or vitamin B12 deficiency
What is the role of vitamin B12 in Methylmalonic Acidemia?
Vitamin B12 is a cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA
What are the key clinical features of Organic Acidemias?
Vomiting, poor feeding, lethargy, seizures, hypotonia, growth faltering, hepatomegaly, and coma
What laboratory findings are associated with Organic Acidemias?
High anion gap metabolic acidosis, hyperammonemia, elevated propionic or methylmalonic acid in urine/serum, and ketonuria
What is the dietary treatment for Organic Acidemias?
Low-protein diet avoiding valine, odd-chain fatty acids, methionine, isoleucine, and threonine (VOMIT)
