Maple syrup urine disease

Last revised by Henry Atkinson on 13 Oct 2024

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 is a very rare disease in the general population, occuring in 1 in 185,000 births, but is much more frequent in certain groups with a high rate of consanguinity, being as common as 1 in 380 births amongst North American Mennonites 9, 10.

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, globi 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.

Cases and figures

  • Case 1
  • Case 2
  • Case 3: with central cerebellar changes
  • Case 4
  • Case 5
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