Decoding Intermediate Maple Syrup Urine Disease Type 2: A Dive into Genetic Testing and Diagnosis

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Intermediate maple syrup urine disease type 2 (MSUD) is a rare, inherited metabolic disorder that affects the body’s ability to process certain amino acids. This can lead to a buildup of toxic substances in the blood and urine, resulting in a range of symptoms, including poor feeding, lethargy, and developmental delays. Understanding, diagnosing, and managing this condition relies heavily on genetic testing, as highlighted in several recent studies.

Understanding Intermediate MSUD Type 2

MSUD is caused by a deficiency in an enzyme called branched-chain alpha-ketoacid dehydrogenase (BCKD). This enzyme is responsible for breaking down three essential amino acids - leucine, isoleucine, and valine. Without proper functioning of BCKD, these amino acids and their toxic byproducts accumulate in the body, causing damage to the brain and other organs.

Intermediate MSUD type 2 is a milder form of the disease, with symptoms typically appearing in early childhood. Children with this condition may experience feeding difficulties, poor growth, and developmental delays, as well as episodes of metabolic crisis triggered by illness or stress. Early diagnosis and treatment are crucial to prevent long-term complications and improve the quality of life for these individuals.

Diagnosing Intermediate MSUD Type 2

Diagnosing intermediate MSUD type 2 can be challenging due to its variable presentation and the rarity of the condition. In a recent case report, an intermediate MSUD case was identified through genetic analysis after initial tests were inconclusive. This highlights the importance of genetic testing in diagnosing ambiguous cases of MSUD.

Genetic Testing for MSUD

Genetic testing for MSUD involves analyzing the DNA for mutations in the genes responsible for the production of BCKD. These genes include BCKDHA, BCKDHB, and DBT. Identifying the specific gene mutations can help confirm the diagnosis, determine the severity of the disease, and guide treatment decisions.

In another study, a novel mutation in the DBT gene was identified as the cause of classic MSUD in an Azerbaijani child, emphasizing the importance of newborn screening tests for early detection and intervention. Furthermore, a case series examining 11 individuals with MSUD of Central American ancestry found two pathogenic variants in the DBT gene, suggesting a possible founder effect in this population.

Benefits of Genetic Testing for MSUD

Genetic testing for MSUD offers several benefits, including:

• Early diagnosis and intervention, leading to improved outcomes and reduced risk of complications.
• Identification of carriers, allowing for informed family planning and genetic counseling.
• Guidance for treatment options, such as dietary management, medications, or liver transplantation.
• Improved understanding of the disease, leading to the development of new therapies and research opportunities.

Treatment and Management of Intermediate MSUD Type 2

There is currently no cure for MSUD, but early diagnosis and treatment can help manage symptoms and reduce the risk of complications. Treatment typically involves a strict, lifelong diet low in leucine, isoleucine, and valine, as well as supplementation with a specialized medical formula. In some cases, medications or liver transplantation may be necessary.

A recent report on five pediatric cases of domino liver transplantation from live donors with MSUD showed successful outcomes, supporting the effectiveness of this treatment approach. Liver transplantation can provide a source of functional BCKD enzyme, improving the body’s ability to process the affected amino acids and reducing the risk of metabolic crises.

In conclusion, genetic testing plays a pivotal role in understanding, diagnosing, and managing intermediate maple syrup urine disease type 2. Early detection and intervention are crucial for improving the quality of life for those affected by this rare metabolic disorder. As our knowledge of the genetic basis of MSUD continues to grow, so too will our ability to develop new treatments and therapies for this challenging condition.

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)