Maple syrup urine disease

Last revised by Osamah A. A. Alwalid on 10 Feb 2022

Maple syrup urine disease (MSUD) is a very rare metabolic disorder. It is an inborn error of amino acid metabolism, which classically affects the brain tissue resulting in impairment or death if untreated.

MSUD occurs in 1 in 185,000 births 9.

It usually manifests itself within the first week of life with 8:

  • poor feeding
  • vomiting
  • ketoacidosis
  • hypoglycemia
  • lethargy
  • seizures
  • characteristic odor of maple syrup in the urine or cerumen

Intermittent forms of the disease may present later (5 months to 2 years of age) and can be precipitated by concomitant infection or a high protein intake 8.

Maple syrup urine disease is due to mutations in any aspect of the mitochondrial branched-chain alpha-keto acid dehydrogenase complex 8

It is inherited in an autosomal recessive pattern and various different genes have been implicated 1.

There is elevated plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine), allo-isoleucine, and alpha-ketoacids.

MRI brain may show the characteristic pattern of edema present in MSUD. Two forms of edema may be seen in MSUD:

  • intramyelinic edema: believed to be from myelin splitting due to accumulation of branched-chain key acids and water molecules between layers of myelin 8
  • vasogenic edema: usually due to disruption of the blood-brain barrier during an acute metabolic crisis or decompensation 8

Signal characteristics include: 

  • T1: low signal intensity
    • predominantly in the cerebellar white matter, cerebral peduncles, dorsal brainstem, posterior limb of the internal capsule, thalami, globe pallidi, and perirolandic cerebral white matter 8
  • T2: high signal intensity
    • in the locations described above 8
  • DWI: the posterior limbs of the internal capsules and optic radiations and the central corticospinal tracts within the cerebral hemispheres exhibit high diffusion signal
  • MR spectroscopy: single-voxel proton MR spectroscopy may show the presence of branched-chain amino acids and branched-chain alpha-keto acids resonating at 0.9-1.0 ppm, especially during a metabolic crisis 1,2

Management involves dietary changes, such as life-long dietary intake restriction of foods with branched-chain amino acids (especially leucine), and early treatment of metabolic decompensation, with agents such as intravenous glucose 9.

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