U01.01.110 Maple syrup urine disease

Maple syrup urine disease (MSUD) is a metabolic disorder caused by a defect in the breakdown of branched-chain amino acids (BCAAs): isoleucine, leucine, and valine. This condition results in the accumulation of α-ketoacids, particularly leucine, in the blood. MSUD is inherited in an autosomal recessive pattern.

Pathophysiology

Cause:
Blocked degradation of branched-chain amino acids due to a deficiency in branched-chain α-ketoacid dehydrogenase (BCKD), which requires thiamine (B1) as a cofactor.
Accumulation of α-ketoacids:
These metabolites build up in the blood, especially those derived from leucine, which leads to clinical manifestations.

Clinical Presentation

Symptoms:
- Vomiting
- Poor feeding
- Urine odor: Characteristic sweet smell resembling maple syrup or burnt sugar
- Severe CNS defects
- Intellectual disability
- Death (if untreated)

Diagnosis

Urine test:
Detection of the characteristic maple syrup odor due to the presence of BCAA metabolites.
Blood tests:
Elevated levels of branched-chain amino acids, particularly leucine.

Treatment

Dietary management:
- Restriction of isoleucine, leucine, and valine in the diet.
- Careful monitoring of amino acid levels.
Thiamine supplementation:
Since BCKD requires thiamine (Vitamin B1) for function, supplementation is crucial for management.

Key Points to Remember

Key Concept	Details
Cause	Blocked breakdown of BCAAs due to branched-chain α-ketoacid dehydrogenase deficiency
Inheritance	Autosomal recessive
Presentation	Vomiting, poor feeding, sweet-smelling urine, CNS defects, intellectual disability
Diagnosis	Elevated BCAA levels in blood, characteristic urine odor
Treatment	Dietary restriction (BCAAs), thiamine supplementation
Mnemonic	“I Love Vermont maple syrup from maple trees (with B1ranches)”

Conclusion

Maple syrup urine disease is a metabolic disorder characterized by the accumulation of branched-chain amino acids and their keto acids in the blood. Early recognition and dietary management, along with thiamine supplementation, are essential to prevent severe neurological damage and death.

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