Maple Syrup Urine Disease (MSUD)

Question 1

A 4-day-old infant is brought to the emergency department due to lethargy, poor feeding, and vomiting. On examination, the infant appears irritable and hypotonic. The parents report that the baby’s diapers have a sweet, “maple syrup-like” odor. Laboratory findings reveal hypoglycemia, metabolic acidosis, and elevated levels of leucine, isoleucine, and valine. Which of the following is the most likely enzyme deficiency in this patient?

A) Branched-chain alpha-ketoacid dehydrogenase
B) Phenylalanine hydroxylase
C) Ornithine transcarbamylase
D) Methylmalonyl-CoA mutase
E) Propionyl-CoA carboxylase

Answer 1

Answer: Branched-chain alpha-ketoacid dehydrogenase

Explanation: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase, resulting in impaired breakdown of branched-chain amino acids (leucine, isoleucine, and valine). The condition presents in the neonatal period with lethargy, vomiting, poor feeding, hypotonia, and the characteristic sweet odor of urine resembling maple syrup. Elevated levels of branched-chain amino acids and their alpha-ketoacids confirm the diagnosis. Treatment involves dietary restriction of branched-chain amino acids and supplementation with thiamine.

Incorrect Answers:

B) Phenylalanine hydroxylase deficiency causes phenylketonuria (PKU), characterized by intellectual disability and a musty odor, not maple syrup-like urine.
C) Ornithine transcarbamylase deficiency causes hyperammonemia and elevated orotic acid without branched-chain amino acid accumulation.
D) Methylmalonyl-CoA mutase deficiency results in methylmalonic acidemia, presenting with metabolic acidosis and hyperammonemia.
E) Propionyl-CoA carboxylase deficiency causes propionic acidemia, which leads to similar symptoms but without the characteristic maple syrup odor or elevated branched-chain amino acids.

Question 2

What is the genetic inheritance pattern of Maple Syrup Urine Disease (MSUD)?

Answer 2

Autosomal recessive

Question 3

What are the main enzymes and genes involved in MSUD?

Answer 3

Deficiency of branched-chain alpha-ketoacid dehydrogenase.

requires B1 (thiamine) coenzyme.

Mutations in BCKDHA, BCKDHB, and DBT genes

Question 4

What is the primary metabolic defect in MSUD?

Answer 4

Impaired breakdown of branched-chain amino acids (BCAA): leucine, isoleucine, and valine

Question 5

What are the clinical features of MSUD?

Answer 5

Within days of birth:
- vomiting, lethargy, poor feeding, dystonia

Leads to:
- intellectual disability, delayed growth, and severe CNS damage due to elevated leucine.
-progressive neurological decline.

Question 6

What is the characteristic odor associated with MSUD?

Answer 6

Sweet-smelling urine resembling maple syrup or burnt sugar

Question 7

What laboratory findings are typical in MSUD?

Answer 7

Increased levels of alpha-ketoacids (especially leucine alpha-ketoacids), elevated levels of leucine, isoleucine, and valine, and hypoglycemia.

Question 8

What is the main dietary treatment for MSUD?

Answer 8

Avoid foods containing branched-chain amino acids (leucine, isoleucine, and valine) and supplement thiamine (a cofactor for the enzyme)

Question 9

What is the treatment of last resort for severe MSUD cases?

Answer 9

Liver transplantation