Maple Syrup Urine Disease

• Context (TH): Gene therapy offers new treatment options for Maple Syrup Urine Disease (MSUD).

About Maple Syrup Urine Disease (MSUD)

• It is a rare genetic disorder where the body cannot metabolise branched-chain amino acids (BCAAs) like leucine, isoleucine and valine due to a deficiency in branched-chain alpha-keto acid dehydrogenase (BCKDH) complex.
• Inheritance Pattern: Autosomal recessive; both parents must carry and pass on the mutated gene for the disease to manifest in offspring.

Types of MSUD

• Classic MSUD: Most severe and common; symptoms appear within the first few days after birth.
• Intermediate MSUD: Less severe than classic; symptoms emerge between 5 months and 7 years.
• Intermittent MSUD: Symptoms triggered by illness or stress; higher BCAA tolerance than classic MSUD.
• Thiamine-Responsive MSUD: Improves with high-dose vitamin B1 (thiamine) and dietary restrictions.

Symptoms of MSUD

• Distinct Odor: Sweet, maple syrup-like smell in urine, sweat, or earwax.
• Neurological Symptoms: Lethargy, irritability, and poor feeding in infants.

• Severe Complications: If untreated, can cause seizures, coma, or death.

Traditional Treatment Approaches

• Dietary Management: Lifelong adherence to a low-protein diet to limit BCAA intake.
• Liver Transplant: A potential cure by introducing functional BCKDH enzymes but carries surgical risks.

Advancements in Gene Therapy

• Recent Developments: A gene therapy using an adeno-associated viral (AAV) vector is developed to deliver functional copies of the BCKDH A and BCKDH B genes.