A 7-day-old neonate born to a 28-year-old woman is brought to the office due to progressive lethargy, vomiting, and poor feeding. The mother reports an uneventful pregnancy and perinatal course. She exclusively breastfeeds the infant and has no medical problems in any of her other children. On examination, the infant is somnolent and dehydrated with decreased muscle tone. Laboratory studies reveal metabolic acidosis with an elevated anion gap, ketosis, and hypoglycemia. Further evaluation reveals a markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA. This patient is most likely unable to use which of the following amino acids for energy production?

Question

A 7-day-old neonate born to a 28-year-old woman is brought to the office due to progressive lethargy, vomiting, and poor feeding.  The mother reports an uneventful pregnancy and perinatal course.  She exclusively breastfeeds the infant and has no medical problems in any of her other children.  On examination, the infant is somnolent and dehydrated with decreased muscle tone.  Laboratory studies reveal metabolic acidosis with an elevated anion gap, ketosis, and hypoglycemia.  Further evaluation reveals a markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA.  This patient is most likely unable to use which of the following amino acids for energy production?

Quizplus · Accepted Answer

11ec160b_36b5_113b_9249_59bd7d97755f_MD0001_00 Catabolism of several essential amino acids (valine, isoleucine, methionine, and threonine) along with odd-chain fatty acids results in the generation of propionyl-CoA. Propionyl-CoA is subsequently converted to methylmalonyl-CoA in a reaction catalyzed by biotin-dependent propionyl-CoA carboxylase. Isomerization of methylmalonyl-CoA then generates succinyl-CoA, which enters the TCA cycle. This patient's presentation is consistent with propionic acidemia, an autosomal recessive organic acidemia caused by congenital deficiency of propionyl-CoA carboxylase. This enzyme catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. In its absence, excess propionic acid accumulates in the bloodstream, causing severe metabolic acidosis. Hypoglycemia and ketosis frequently develop secondary to the acidosis. Affected patients present 1-2 weeks after birth with lethargy, poor feeding, vomiting, and hypotonia. Treatment involves starting a low-protein diet containing minimal amounts of valine, isoleucine, methionine, and threonine. (Choice A) Alanine transaminase catalyzes the transfer of an amino group from alanine to α-ketoglutarate, generating pyruvate that can be used for gluconeogenesis. (Choice B) Aspartate is a nonessential amino acid; it can be converted into oxaloacetate for use in the TCA cycle by aspartate transaminase. (Choice C) Glutamate is deaminated by glutamate dehydrogenase to form the TCA cycle intermediate α-ketoglutarate. (Choice D) Lysine and leucine are essential amino acids that are strictly ketogenic. They are metabolized into acetyl-CoA, which is a precursor for ketone bodies. (Choice E) Phenylalanine is converted to tyrosine by the enzyme phenylalanine hydroxylase. Tyrosine is further converted into fumarate (TCA cycle intermediate) and acetoacetate (ketone body). Educational objective: Propionyl-CoA is derived from the metabolism of valine, isoleucine, methionine, threonine, and odd-chain fatty acids. Congenital deficiency of propionyl-CoA carboxylase, the enzyme responsible for the conversion of propionyl-CoA to methylmalonyl-CoA, leads to the development of propionic acidemia. The condition presents with lethargy, poor feeding, vomiting, and hypotonia 1-2 weeks after birth.

A 7-Day-Old Neonate Born to a 28-Year-Old Woman Is Brought