Remember when no one ever heard of MSUD? Now it’s encouraging to see how clinicians and researchers from all around the world are looking for ways to improve treatment. Here is a brief report on several recent publications.

Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino acid mixture.

A french group studied the outcome when very high leucine levels were treated with a branched-chain amino acids free intravenous solution (TPN) in individuals with MSUD ages 21-31, and compared this with outcomes in the same individuals who had been treated with enteral formula by tube feeding in prior years.

In their hospital, patients are hospitalized when levels are above 763 mmoles per liter or 10 mg/dL, and receive dialysis to rapidly reduce levels when above 1526 mmoles/liter or 20 mg/dL. The researchers found that the drop in leucine levels was significantly greater when patients received parenteral nutrition (through the veins) as compared with enteral formula feeding. Leucine levels normalized within 3.5 days when patients received parenteral nutrition, while patients tended to leave the hospital against medical advice prior to normalization of levels when receiving enteral feedings. In one case, a patients on enteral feedings required dialysis when neurological symptoms occurred.

The researchers concluded that patients in metabolic decompensation tolerated parenteral feedings better enteral, were more likely to have normalized leucine levels upon discharge from the hospital, and that this method of treatment is likely to reduce the risk of complications from very high leucine levels.

Through private correspondence, Dr Aude Servais has said that they also use parenteral nutrition with children who are unable to tolerate oral or tube feeds and have had good results.

Patterns of brain injury in inborn errors of metabolism

Metabolic decompensation in MSUD causes brain injury, cerebral edema, and can be fatal.

In this paper Dr.Gropman of the department of Neurology at Children’s National Medical Center in Washington, DC, discusses pathways by which this occurs and the importance of brain imaging in the treatment of MSUD.

The blood brain barrier (BBB) is a network of cells in the blood vessels of the brain which control which substances can enter the brain. The BBB allows nutrients to enter the brain while preventing the entry of harmful substances. Dr. Gropman suggests that variability in the BBB is responsible at least in part for the variability observed in clinical manifestations, perhaps making some individuals more susceptible to brain injury than others.

Low levels of serum sodium, which may occur as a results of repeated vomiting, increases the risk of cerebral edema. Sodium is instrumental in determining the amount of fluid which enters the brain. When sodium levels are low, water may be pulled from the blood vessels into the cells of the brain. This edema can be seen with MRI, making this an important tool in monitoring the response of the brain to high levels of leucine and the response to treatment.

Domino Liver transplantation in maple syrup urine disease: a case report and review of the literature

Badell and colleagues describe their experiences at the Emory Transplant Center with domino transplantation. The livers of individuals with MSUD are seen as a potential source of livers which can be used to save the lives of those suffering from end stage liver disease. In their case study, the authors describe domino transplantation in which a liver was transplanted into an MSUD patient, and the liver from the MSUD patient was transplanted into a man born with hemophilia who contracted HIV and hepatitis from contaminated blood. This man was a low priority on the waiting list despite declining quality of life, and had been waiting for a liver for 6 years. At 30 months post-transplant, the MSUD patient has near normal levels of branch-chain amino acids while the liver patients has been cured of hemophilia and does not have clinical signs of MSUD.

  • Servais A, Arnoux JB, Lamy C et al Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino-acid misture. Journal of Inherited Metabolic Diseases (2012) epublished ahead of print
  • Gropman AL Patterns of brain injury in inborn errors of metabolism. Sminars in Pediatric Neurology 2012 Dec; 19(3):203-10.doi:10.1016/j.spen.2012.09.007.
  • Badell IR, Hanish Sl, Hughes CB et al Domino Liver Transplantation in Maple Syrup Urine Disease: A Case Report and Review of the Literature.
  • Transplantation Proceedings (2012) Sep 6. pii:S0041-1345(1200661-6.doi:10.1016/j.transproceed.2012.04.031. [Epub ahead of print]