Medical mystery Solved

During Sean’s illness his family frantically searched the internet hoping to find a cause.  As we now have the answers we hope to raise awareness of un-diagnosed inborn metabolic disorders and acute metabolic illness which may appear as neurological or psychiatric.

Rare, life-threatening metabolic diseases are normally diagnosed in childhood. Andrea and Sean’s story challenges the current assumption that these illnesses manifest only in children. Each of these siblings became ill in their 30s . They had no previous episodes of confusion/delusions and in fact had mostly unremarkable medical histories. Also see the Soldier’s Story on the Resources page.

As Andrea’s illness progressed, she was diagnosed with encephalitis.  After her death, the Medical Examiner’s office reported that she did not have encephalitis but rather encephalopathy. The family later discovered that according to Johns Hopkins Medicine, 50% of deaths attributed to encephalitis have an undetermined cause. The other 50% are attributed to either viral, bacterial of auto-immune causes. Could some portion of these un-diagnosed cases be due to metabolic illness? We believe this possibility should be studied.

The Diagnosis of rare metabolic childhood disorder -MSUD

Once the hospital broadened its investigation, metabolic panel testing revealed a surprising result.  Sean’s branch chain amino acid levels were extremely high – a hallmark of MSUD – Maple Syrup Urine Disease. A provisional diagnosis was made and was later confirmed by DNA testing. 

MSUD as well as other metabolic disorders, are diagnosed in early childhood and is typically discovered through newborn screening.  It is virtually unheard of for an adult to be diagnosed with this disorder, and yet, this is exactly what Sean’s case revealed.

This remarkable finding was passed along to the Medical Examiner looking at Andrea’s case, who determined that Andrea also had MSUD. The cause of the encephalitis / encephalopathy leading to her death was acute, undiagnosed metabolic crisis due to complications from MSUD.

The family was informed by the internal medicine doctor that no hospital, anywhere in the world, would ever be familiar with this life-threatening rare inborn metabolic disease unless the patient was in a pediatric setting, in a specialized rare disease hospital or in a Children’s Hospital.

Initial research by the family identified the oldest patient diagnosed with MSUD disease was a 7-year-old. Subsequent research found a case in China of an 8 year old. Anecdotal stories from the MSUD support group website, out of the USA, has a group member sharing that they were diagnosed at 15-years-old after years of unexplained illness.  Andrea and Sean may be the first adults in the world to be diagnosed with MSUD. 

Each parent must be a carrier (autosomal) of the recessive gene for offspring to be a carrier or have the disease. There is a higher prevalence of MSUD in Old Order Mennonite population and French-Canadian ancestry. Andrea and Sean had no known family history of this disease.

The specialists involved in Sean’s care have expressed that the experience of Sean’s illness and the family’s advocacy has humbled them. They have also expressed that Sean’s life was saved due to his sister’s passing and his family’s persistent advocacy.