Maple Syrup Urine Disease Awareness Day Date in the current year: June 16, 2025

Maple syrup urine disease (MSUD) is an inherited condition caused by a mutation in one of four genes: BCKDHA, BCKDHB, DBT, and DLD. These genes encode proteins that work together as the branched-chain α-ketoacid dehydrogenase (BCKD) complex, which breaks down branched-chain amino acids (BCAAs) – leucine, isoleucine, and valine. These amino acids are present in most foods, especially protein-rich ones.

MSUD-associated mutations prevent the BCKAD complex from functioning normally. This results in a buildup of BCAAs and their toxic byproducts in the blood and urine. This buildup makes the urine and earwax smell like maple syrup, hence the name of the disease, and causes various neurological symptoms.

There are five main types of MSUD based on residual BCKAD enzyme activity, time of onset, and severity of symptoms: classic (little to no activity); intermediate (3% to 30% activity); intermittent (5% to 20% activity); thiamine-responsive (2% to 40% activity); and E3-deficient (varying levels of enzyme activity).

Classic MSUD is the most common form; its symptoms begin to develop within the first 24 to 48 hours of life. Apart from the smell of the urine and earwax, the symptoms of MSUD are mostly neurological and nonspecific. These symptoms include irritability, lethargy, vomiting, feeding problems, abnormal movement, muscle rigidity, and, as the levels of amino acids and their by-products increase in the body, seizures and coma. Without treatment, classic MSUD causes progressive brain damage and eventually death.

Intermediate MSUD is a much milder form that typically presents between five months and seven years of age. Symptoms include growth and developmental delays, poor appetite, and poor intellectual progress. Intermittent, thiamine-responsive, and E3-deficient MSUD are rare forms of this already rare disease.

For patients with classic MSUD, it is crucial to lower BCAA levels as soon as the diagnosis is confirmed. Acute management includes intravenous infusions of glucose and lipids, and sometimes insulin. It also includes the rapid removal of excess leucine through methods such as exchange transfusion, hemodialysis, or hemofiltration. Thiamine-responsive MSUD responds to treatment with thiamine (vitamin B1), as its name suggests.

Patients with MSUD should adhere to a lifelong low-protein diet to prevent the buildup of BCAAs and metabolic crises. Since leucine, isoleucine, and valine-rich products also contain essential nutrients, such as other amino acids, vitamins, minerals, and omega-3 fatty acids, patients may require dietary supplements to meet their nutritional needs. Although liver transplantation can normalize metabolic function and eliminate the need for a special diet, it is a high-risk procedure.

Maple Syrup Urine Disease Awareness Day was created to raise awareness of this rare disease, support affected patients, and advocate for research into therapies and, ideally, a cure.