Medical Care
The two main approaches to the treatment of maple syrup urine disease (MSUD) include (1) long-term daily dietary management and (2) treatment of episodes of acute metabolic decompensation.
The mainstay in the treatment of maple syrup urine disease is dietary restriction of branched-chain amino acids (BCAAs). [9, 18, 16] Consultation with a neonatal/pediatric nutritionist with expertise in dietary management of metabolic disorders is required to address medical nutrition therapy immediately.
The goals of medical nutrition therapy in maple syrup urine disease are multifaceted, as follows [19] :
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To rapidly reduce toxic metabolites by restricting dietary BCAAs to amounts allowing patients to achieve and maintain plasma BCAA concentrations within the targeted treatment ranges
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To reduce catabolism
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To promote anabolism
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To monitor nutritional status and alter intake to promote and sustain normal growth
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To enable normal development and health maintenance
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To evaluate thiamine responsiveness if the patient has residual BCKD activity and to administer thiamine supplements if the patient is responsive
Aggressively treat episodes of metabolic decompensation. Initiate intravenous glucose infusions (5-8 mg/kg/min for infants) as rapidly as possible. Insulin infusions may be added to promote anabolism. Stop intake of BCAAs but resume intake as soon as plasma BCAAs normalize. Whenever possible, continue additional dietary support, including lipids and/or nutrition free of BCAAs. In rare circumstances, hemodialysis or peritoneal dialysis is required to remove BCAAs and keto acids.
Initial studies using retroviral vectors to infect maple syrup urine disease lymphocytes have shown stable correction of the enzyme deficiency. However, human gene therapy trials for maple syrup urine disease have yet to be performed.
Several successful pregnancies in patients with maple syrup urine disease have been reported. The most critical period for metabolic management is during the immediate postpartum period. Take particular care to counteract catabolism during this time.
Surgical Care
Orthotopic liver transplantation performed at an experienced medical center has changed the outlook for patients with classic maple syrup urine disease, who are frequently challenged with episodes of metabolic decompensation. It appears that, while liver transplantation cannot reverse the neurological damage that has already occurred, it can prevent additional episodes of decompensation and preserve the remaining neurological function.
Three successful liver transplantations in patients diagnosed with classic maple syrup urine disease have been reported. [20] A 2012 study reported that patients who were mentally impaired prior to transplantation had no change in their neurocognitive function one year later. These results suggest that liver transplantation may be an effective treatment for classic maple syrup urine disease, and, although it may arrest further brain damage, it cannot reverse it. [21]
Liver transplantation may guarantee normal or near-normal neurological outcomes if performed early following diagnosis. [21] Certainly, the objective is to prevent the need for liver transplantation in newborns diagnosed with maple syrup urine disease by immediately fostering early dietary intervention of BCAAs restriction.
Diet
The goal of dietary therapy is normalization of branched-chain amino acids (BCAAs), leucine in particular, by restricting intake of BCAAs without impairing growth and intellectual development. Dietary therapy must be lifelong. Several commercially available infant formulas (ie, BCAD 1) and foods for all ages (ie, Nutricia products, MSUD Express) are available without BCAAs or with reduced levels of BCAAs. Lifelong nutritional guidance is imperative.
For patients with maple syrup urine disease, the intake of leucine is calculated on an individual basis following measurement of plasma BCAAs. Measure plasma BCAAs levels on a regular basis at appropriate intervals for the first 6-12 months of life. In addition to dietary therapy, consider thiamine (10-20 mg/d) for 4 weeks to determine thiamine responsiveness.
Activity
Do not restrict activity.
Prevention
Patients should avoid consuming branched-chain amino acids (ie, natural protein) in excess of their daily allowance.
Long-Term Monitoring
Follow up with the patient at regular intervals (ie, at least once every 6-12 mo) with a biochemical geneticist familiar with the management of maple syrup urine disease. Seek dietary guidance with a nutritionist knowledgeable in dietary management of metabolic disorders. Emphasize the importance of continuity of care with a pediatrician/developmental pediatrician to closely follow developmental milestones and neurocognitive function.
