Maple syrup urine disease (MSUD) is a rare inherited disorder of branched-chain amino acid metabolism classically characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated.
MSUD follows a pattern autosomal recessive inheritance. The estimated prevalence is around 1/150,000 live births.
There are five different clinical phenotypes: classic, intermittent, intermediate, sensitive thiamine and E3 deficient. In most cases, they do not correlate with specific mutations. However, they can be distinguished based on the age of onset, severity of clinical symptoms and response to treatment with thiamine.
Classic MSUD presents in the first days of life with poor feeding and drowsiness followed by a worsening encephalopathy with lethargy, intermittent apnea, stereotypic movements ("fencing" and ''bicycling") and opisthotonus. Coma and central respiratory failure supervene 7 to 10 days after birth. The only abnormality in biochemistry is ketosis. Intermediate MSUD clinically resembles classic MSUD but it can have a later onset and less severe symptoms. Intermittent MSUD patients are asymptomatic at birth but may suffer episodes of acute decompensation or develop neurological symptoms and developmental delay during childhood. Thiamin-responsive MSUD is clinically similar to intermediate MSUD with thiamin therapy improving dietary leucine tolerance. E3 deficiency has been reported in a single case of mild intermediate MSUD.