From the Guidelines
The enzyme deficient for the inability to oxidize branched-chain amino acids (BCAAs) when combined with high intake of green leafy vegetables is branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, which causes Maple Syrup Urine Disease (MSUD) 1. This enzyme deficiency is a genetic disorder where the body cannot properly break down the amino acids leucine, isoleucine, and valine. When someone with MSUD consumes high amounts of protein-rich foods, including green leafy vegetables, the BCAAs accumulate in the blood because the defective BCKDH enzyme cannot catalyze their oxidative decarboxylation. This accumulation leads to neurological symptoms and can be life-threatening if untreated. The condition requires careful dietary management with restricted protein intake, especially limiting foods high in BCAAs, and sometimes supplementation with a specialized formula. Key points to consider in managing this condition include:
- Careful planning of elective hospitalizations or procedures that require fasting, with proper intravenous glucose support and metabolic monitoring 1
- Consideration of liver transplantation in patients with frequent episodes of metabolic decompensation, uncontrollable hyperammonemia, restricted growth, or severe impairment of health-related quality of life with conventional medical treatment 1, 2
- Evaluation of the reversibility of the enzyme deficiency with whole or partial organ liver transplantation, and estimation of the potential for functional health after transplantation 2
From the Research
Enzyme Deficiency and Branched-Chain Amino Acids
- The enzyme deficient in the inability to oxidize branched-chain amino acids (BCAAs) is the branched-chain α-keto acid dehydrogenase complex (BCKDC) 3, 4, 5, 6.
- BCKDC is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of the branched-chain α-keto acids derived from leucine, isoleucine, and valine 6.
- Deficiency in BCKDC leads to the accumulation of BCAAs and their respective α-keto acids, resulting in maple syrup urine disease (MSUD) 3, 4, 5.
Pathophysiology of Maple Syrup Urine Disease
- MSUD is an autosomal recessive disorder that affects the catabolism of BCAAs, leading to their accumulation in tissues and urine 3, 4, 5.
- The accumulation of BCAAs and their α-keto acids can cause neurotoxic effects, leading to brain damage and neurological symptoms such as seizures, coma, and intellectual disability 3, 4.
- The pathophysiology of MSUD involves the disruption of brain amino acid homeostasis, leading to impaired cerebral protein and neurotransmitter synthesis 3.
Treatment and Management of MSUD
- Treatment of MSUD typically involves dietary restriction of BCAAs and liver transplantation to restore functional BCKDC activity 4, 5.
- Despite advances in clinical care, MSUD remains a morbid and potentially fatal disorder, with significant cognitive and psychiatric morbidities remaining in affected patients 5.
- There is a critical need for safe and effective disease-modifying therapies for MSUD, which can be implemented early in life to prevent long-term neurological sequelae 5.