[3 patients with maple syrup urine disease]

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited metabolic disorder.
• It is characterized by a deficiency in the branched-chain alpha-keto acid dehydrogenase complex, leading to the accumulation of branched-chain amino acids (BCAAs) and their alpha-ketoacids.
• This accumulation causes severe neurological damage and developmental delay if left untreated.

Observation:

• Three patients diagnosed with classical type I MSUD presented with early-onset clinical symptoms.
• Diagnosis was confirmed by detecting high concentrations of leucine, isoleucine, valine, and their alpha-ketoacids in plasma and urine.
• Patients also exhibited a characteristic odor and progressive neurological alterations.

Findings:

• The patients demonstrated a very reduced rate of leucine decarboxylation in cultured fibroblasts, consistent with classical MSUD.
• Despite exhibiting classical symptoms, none of the patients responded favorably to suprapharmacological doses of thiamine.
• Treatment strategies were discussed and compared with existing literature recommendations.

Implications:

• This case series highlights the diagnostic criteria and clinical variability of classical MSUD.
• The lack of response to thiamine in these patients underscores the need for individualized treatment approaches.
• Further research into alternative or adjunctive therapies for MSUD is warranted to improve patient outcomes.