A 3-day-old female infant presents with poor feeding, lethargy, vomiting after feeding, and seizures. Labs revealed ketoacidosis and elevated hydroxypropionic acid levels. Upon administration of parenteral glucose and protein devoid of valine, leucine, methionine, and threonine, and carnitine, the infant began to recover. Which of the following enzymes is most likely deficient in this infant?
1.Branched-chain ketoacid dehydrogenase
2.Phenylalanine hydroxylase
3.Propionyl-CoA carboxylase
4.Cystathionine synthase
5.Homogentisate oxidase
exp:
This newborn has elevated levels of hydroxypropionic acid and symptoms suggestive of propionic acidemia. Propionyl-CoA carboxylase is deficient in this patient.
Propionic acidemia is an autosomal recessive disorder caused by a deficiency of propionyl-CoA carboxylase in the propionic acid cycle. This deficiency results in the inability to metabolize VOMIT via the propionic acid cycle:
-Valine
-Odd-chain fatty acids (proprionic acid)
-Methionine
-Isoleucine
-Threonine
Patients present with ketoacidosis and have elevated blood levels of propionic acid, methyl citrate, and hydroxypropionic acid. Other defects of propionic acidemia include methylmalonyl-CoA mutase deficiency which results in elevated methylmalonic acid levels.
Carrillo-Carrasco and Venditti review propionic acidemia, in particular the neonatal form. Symptoms begin within the first days of life including poor feeding, vomiting, and excessive sleepiness. Symptoms progress to seizures, lethargy, and coma and ultimately death. Propionic acidemia displays metabolic acidosis with anion gap, hypoglycemia, hyperammonemia, and ketonuria.
Deodato et al. discuss the treatment of propionic acidemia. Treatment consists of maintaining a low protein diet especially low in methionine, threonine, isoleucine, and valine. IV carnitine is useful as this helps to buffer the increased levels of mitochondrial propionyl-CoA.
Illustration A depicts the proprionic acid cycle.