It was the resident’s third or fourth day without an answer when someone on the team suggested consulting the metabolism service. Metabolic diseases are disorders that interrupt the processes that turn food into energy at the cellular level. Most of these disorders are inherited — caused by genetic mutations that alter the structure or function of one of the body’s tools needed to metabolize carbohydrates, fats, proteins and other nutrients. And while most of these diseases are rare, there are many of them. It is estimated that metabolic diseases affect up to one in 1,000 people. Still, most show up in infancy or childhood, not at age 35.
The neurology resident called a friend on the metabolism service, Dr. Tyler Peikes, who immediately went to see Sean. He reviewed the records, examined the patient and got the story from Sean and his family. It didn’t sound like any of the metabolic diseases he knew. The rapid course of the sister’s illness was uncharacteristic. He ordered tests to look for those diseases that usually appear intermittently.
The neurology resident continued to look for answers. And slowly the results trickled in. It wasn’t an exposure to a metal like arsenic or mercury. It wasn’t an autoimmune disease. It wasn’t an infection. At the end of each day, the resident made another X on her calendar and went home worried. The only hopeful sign was that the patient’s episodes were becoming less frequent. She wasn’t sure why but hoped it meant they would have enough time.
Ordering the Right Test
Finally, on Day 11, one of the tests that Peikes ordered came back positive. The patient had a rare form of a rare disorder called maple syrup urine disease (M.S.U.D.). Patients with M.S.U.D. are born with abnormalities in the machinery used to break down certain amino acids, the building blocks of proteins. This causes the accumulation of unmetabolized protein components, which can damage the body. Untreated, the disease can result in significant, often fatal swelling of the brain. The name comes from the smell of maple syrup in urine and sweat sometimes caused by the buildup of amino acids during episodes of protein overload. The patient never experienced this.
The frequency of a patient’s attacks, and the age at which they begin, depend on how badly the machinery is broken. In intermittent M.S.U.D. — the version this patient had — the body can handle low levels of amino acids, but a high-protein meal or severe physiological stress can overwhelm the system and allow toxic components to build up. A simple blood test provided the answer. Eventually genetic testing revealed the specific defect. A subsequent test on Andrea’s tissue revealed the same abnormality. Patients with M.S.U.D. must maintain a low-protein diet. That’s the only way to prevent these crises.
It has been more than two years since Sean got his diagnosis. 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. It was Sean’s family that brought this story to my attention. His mother hoped that by sharing her children’s story she could help doctors and families consider the possibility of these rare metabolic diseases when patients present with a psychiatric or neurological disease that no one can figure out. “It’s not a hard test,” the mother said. “You just have to think of it.”