Just months after his sister passed away from a mysterious illness, a 35-year-old man, Sean, was rushed to the ED with similar symptoms. But this time, after checking off psychological problems and a host of potential medical issues, doctors were finally able to diagnose both siblings' "rare form of a rare disorder," Lisa Sanders writes for the New York Times.

Mysterious symptoms plague sister and brother

Sean's sister, Andrea, was admitted to a hospital after experiencing intermittent episodes of severe confusion. Twelve days later, she passed away from her illness. According to the siblings' mother, "[n]o one understood what her daughter had or why she died," Sanders writes.

As a result, when Sean began experiencing similar episodes of confusion three months later, his family immediately had him evaluated at a nearby ED, which ran a few "unrevealing" tests and sent him home. But then, just hours later, Sean experienced another episode. This time, his family took him to Health Sciences Center Emergency Department, the biggest hospital in Winnipeg, Manitoba. His mother refused to let providers send him home this time, explaining to the doctors what had so recently happened to his younger sister.

Struggling to identify a cause

With that history in hand, Sean's doctors decided to admit him for observation for a few days, during which time he experienced several of the disorienting episodes. The doctors sent him for dozens of tests, including an MRI, head CT scans, a spinal tap, and blood tests. But when none of those tests provided any insight, doctors "worried that [Sean] had been so emotionally traumatized by his sister's sudden death that he developed psychological symptoms, something known as conversion disorder."

When Sean’s doctors sent him for psychiatric evaluation, his psychiatrist, Kenneth Zimmer, noticed "how normal [Sean] seemed between those episodes of confusion and fear," Sanders writes. Despite the fact that all the tests—including partial data from a somewhat blurry MRI and an interrupted EEG—had turned up normal results, Zimmer strongly suspected that it wasn't a psychiatric disease.

Finally, a 'clearly abnormal' test result

Ultimately, providers sent Sean for another EEG, and while he moved too much to see a lot, "what could be seen was clearly abnormal," Sanders writes. Similarly, a second MRI showed "a subtle abnormality in a region called the pons that was just like the one noted in Andrea's imaging."

Sean's neurology team had never seen anything like this. Another three or four days passed before the team—constantly brainstorming possibilities—thought about reaching out to Tyler Peikes, a provider on the metabolism service, to see if Sean might be suffering from a metabolic disease.

But metabolic diseases are often spotted in infancy or childhood, not at age 35. And Peikes, for his part, said Sean's condition didn't sound like any of the diseases he was familiar with. Still, Peikes began ordering tests for metabolic diseases that tend to present intermittently.

A 'rare form of a rare disease'

"Finally, on Day 11, one of the tests that Peikes ordered came back positive," Sanders writes. Sean—and, as subsequent testing revealed, his sister—had a "rare form of a rare disorder called maple syrup urine disease" (MSUD).

According to Sanders, patients with this condition cannot effectively break down certain amino acids, the building blocks for proteins, which can—for some patients—result in a maple syrup-like smell in patients' urine and sweat. If left untreated, the body's accumulation of unmetabolized protein compounds can eventually cause "significant, often fatal swelling of the brain," Sanders writes.

Ultimately, the frequency of an MSUD patient's episodes, and the age at which they start, "depend on how badly the machinery is broken," Sanders writes. For Sean, who had so-called "intermittent MSUD," low levels of amino acids were tolerable, "but a high-protein meal or severe physiological stress [could] overwhelm the system and allow toxic components to build up." As a result, Sean, like other MSUD patients, "must maintain a low protein diet," Sanders writes.

"It has been more than two years since Sean got his diagnosis," Sanders writes. "He says he misses the occasional steak or burger, but the memory of what happened to him and his sister is enough to keep him away" (Sanders, New York Times, 3/17).