Unlocking the Mysteries of Type II Maple Syrup Urine Disease: A Guide to Understanding, Diagnosing, and Utilizing Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Maple syrup urine disease (MSUD) is a rare metabolic disorder that affects the body’s ability to process certain amino acids, leading to a buildup of toxic substances in the blood and urine. This can result in a range of symptoms, from poor feeding and lethargy in infants to neurological problems and developmental delays in older children. Thiamine-responsive, type II MSUD is a specific form of this disease that responds to treatment with thiamine (vitamin B1). In this article, we will delve into the details of this condition, explore the diagnostic process, and discuss the role of genetic testing in managing and treating type II MSUD.

Understanding Type II Maple Syrup Urine Disease

Type II MSUD, also known as E2 transacylase-deficient MSUD, is caused by mutations in the E2 transacylase gene. These mutations lead to a deficiency in the enzyme branched-chain alpha-keto acid dehydrogenase (BCKD), which is responsible for breaking down branched-chain amino acids like leucine, isoleucine, and valine (1). When the BCKD enzyme is not functioning properly, these amino acids and their byproducts build up in the body, causing the characteristic sweet-smelling urine and other symptoms of MSUD (2).

Thiamine-responsive type II MSUD is unique in that it can be treated with high doses of thiamine, which helps to restore some of the BCKD enzyme’s function. However, not all individuals with type II MSUD respond to thiamine treatment, making it essential to accurately diagnose the condition and determine the most appropriate course of therapy (1).

Diagnosing Type II Maple Syrup Urine Disease

Diagnosing type II MSUD typically begins with a clinical assessment of symptoms, which may include poor feeding, lethargy, and developmental delays. Blood and urine tests can help to identify the presence of elevated branched-chain amino acids and their byproducts, providing further evidence of the disorder (4).

Genetic Testing for Type II MSUD

Genetic testing is a crucial tool in diagnosing type II MSUD and determining the most effective treatment plan. By analyzing the E2 transacylase gene, doctors can identify the specific mutations responsible for the condition and predict whether an individual is likely to respond to thiamine treatment (1).

For example, a study of individuals with MSUD of Central American ancestry found that two specific pathogenic variants in the DBT gene were responsible for the disease in this population, suggesting a possible founder effect (3). Identifying these variants through genetic testing can help to confirm a diagnosis of type II MSUD and inform treatment decisions.

Benefits of Genetic Testing for Type II MSUD

There are several benefits to using genetic testing for type II MSUD, including:

• Confirming a diagnosis: Genetic testing can provide definitive evidence of type II MSUD, allowing for a more accurate diagnosis and appropriate treatment plan.
• Identifying thiamine responsiveness: By pinpointing the specific mutations responsible for the condition, genetic testing can help predict whether an individual will respond to thiamine treatment.
• Family planning: For families with a history of type II MSUD, genetic testing can provide valuable information about the risk of passing the condition on to future generations.
• Early intervention: In some cases, genetic testing can identify type II MSUD before symptoms develop, allowing for early intervention and treatment to prevent or minimize complications.

In conclusion, type II maple syrup urine disease is a rare metabolic disorder that can have severe consequences if left untreated. By understanding the underlying genetic causes, doctors can diagnose the condition more accurately and develop personalized treatment plans that take into account an individual’s unique genetic makeup. Genetic testing plays a critical role in this process, helping to unlock the mysteries of type II MSUD and improve the lives of those affected by this challenging disease.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)