[The intermediate form of maple syrup disease].

Area of Science:

• Biochemistry
• Neurology
• Genetics

Background:

• Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder affecting branched-chain amino acid metabolism.
• It is characterized by the accumulation of branched-chain amino acids and their ketoacids, leading to neurological damage.

Observation:

• A child with severe developmental delay and spasticity died from respiratory infection, with autopsy revealing spongy brain degeneration.
• Similar clinical and biochemical findings, including reduced branched-chain ketoacid decarboxylase activity, were identified in a younger sister.
• Electron microscopy revealed spongy myelinopathy as the cause of degeneration in MSUD, distinct from Canavan disease.

Findings:

• Post-mortem analysis confirmed an inborn error of amino acid metabolism, consistent with an intermediate variant of leucinosis (MSUD).
• The younger sister, diagnosed with MSUD, showed significantly reduced branched-chain ketoacid decarboxylase activity (3-4% of normal).
• A protein-restricted diet in the younger sister led to improved cerebral development and computer tomography results.

Implications:

• This study highlights the importance of early diagnosis and dietary intervention in managing MSUD.
• The findings differentiate the neuropathology of MSUD from other leukodystrophies like Canavan disease.
• Understanding the specific myelinopathy in MSUD can inform future therapeutic strategies for this metabolic disorder.