The patient, a 7-day-old newborn, looked as healthy as could be when he showed up at the Hopkins Children’s emergency department. He had come into the world via a normal vaginal delivery at 2.75 kilograms, had no family history of metabolic or genetic disorders, and suffered no visible symptoms aside from losing a little weight and sleeping more than usual in the previous 24 hours. On exam, his vitals were normal with the exception of a slightly elevated respiratory rate; his neuorologic evaluation showed all the appropriate reflexes. 

“He appeared well, easily arousable and consolable,” said pediatric resident Sarah Kachan-Liu. 

So why was he in the ED? 

The answer was in his newborn screen, which showed abnormally high levels of valine and leucine, so-called branched chain amino acids (BCAAs). What did the lab results point to? Hint: something you'd likely find in Vermont. 

“We were worried that this child had maple syrup urine disorder (MSUD),” Kachan-Liu said, “unless there was a false positive in the newborn screen.” 

There wasn’t, as follow-up tests at Hopkins revealed valine at 944, four times its normal level of 202, and leucine well above its mean level. The numbers for these BCAAs, said pediatrician and geneticist Hilary Vernon, were indeed diagnostic for MSUD, an autosomal recessive disorder first identified by Johns Hopkins neurologist John Menkes. In 1954 he reported four infants from one family who had all succumbed to the disease, and who all shared a common symptom – urine that smelled like burnt sugar and maple syrup. Hence the hallmark sign and name of the disorder. 

“Patients may have no abnormalities on routine clinical testing,” said Vernon, “but they can have this sweet or syrup-like body and urine odor.” 

Though rare, affecting 1 in 120,000 to 500,000 people, MSUD can be lethal if undetected and untreated. The disruption in the metabolism of the BCAAs and the resulting buildup of ketoacids can result in irritability and poor feeding by age 2-3 days, deepening encephalopathy by age 4-5 days, and coma and central respiratory failure by age 7-10 days. 

“The typical presentation is a normal pregnancy, birth and one to two weeks of life, followed by a progressive toxic encephalopathy with ketosis,” Vernon said. “Some children may present later if they have less severe enzyme deficiencies, which is something to consider in children with episodic neurologic disease who have not been screened in the newborn period,” Vernon added, noting that today every state in this country screens for MSUD. 

The good news is the mainstay treatment, long-term dietary management providing enough BCAAs for protein accretion and growth but not enough to trigger toxic metabolite accumulation, is effective. Pediatricians do have to monitor families frequently for compliance. Just as crucial, Vernon added, is emergency care. 

“When these patients get sick and start breaking down endogenous tissues they’re freely and uncontrollably releasing these amino acids that are poison to their body,” Vernon said. “Neurologic decompensation can occur very quickly and create irreversible consequences, so it’s very important to control the situation as fast as its happening.” 

In this case the infant was given formula without the problematic amino acids. The result? His BCAAs decreased to normal levels over 10 days prior to discharge. “A pretty significant decompensation,” said Kachan-Liu, “was avoided.” 

Click here for more information on MSUD.