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At two years of age, fraternal twins Alexis and Noah Beery had not met most of their developmental milestones and had such poor muscle tone they could barely walk or sit on their own. Noah drooled and vomited continually, and Alexis suffered from body tremors during which her eyes would roll back in her head for hours at a time.

An MRI scan had revealed damage in the periventricular area of Noah’s brain, which led to a diagnosis of cerebral palsy. But children with cerebral palsy tend to improve with treatment; in contrast, the twins’ conditions, particularly Alexis’s, worsened over time...

The twins’ mother, Retta Beery, was most puzzled by the fact that Alexis’s symptoms seemed to fluctuate during the day...

Tired of bouncing around from specialist to specialist, Retta embarked on an exhaustive review of the medical literature. Then, one spring night in 2002, she stumbled upon an old photocopy of a 1991 Los Angeles Times article that described a young girl whose condition had uncanny parallels with Alexis’s...

John Fink, a neurologist at the University of Michigan, had determined ...The fluctuations in her symptoms instead were due to a rare and poorly understood genetic disorder called dopa-responsive dystonia (DRD)—a movement disorder caused by a deficiency in the neurotransmitter dopamine.

Five weeks later, Alexis and Noah were in Fink’s office, and the doctor prescribed Alexis a daily dose of levodopa (a synthetic dopamine).

“That was the first night in Alexis’s life that she slept through the night,” a tearful Retta says. In fact, the following days were filled with many firsts for the five-year-old girl..

A few months later Noah’s right foot started to turn in and his head involuntarily tilted down. Beery and Fink recognized it as the onset of DRD and started him on levodopa as well. Not only did the drug correct his posture, but after six years of vomiting every day, “Noah stopped throwing up,” his mother recalls. Except for taking medication, the twins began living normal, active lives, playing sports and excelling in school.

B

In the fall of 2010...The researchers found that the twins were compound heterozygous: each inherited a nonsense mutation from the mother and a missense mutation from the father, with both mutations occurring in different regions of the gene that codes for the enzyme sepiapterin reductase (SPR), which catalyzes the production of a cofactor—tetrahydrobiopterin (BH4)—necessary for the synthesis of the neurotransmitters dopamine and serotonin.

Not only were the twins deficient in dopamine, but they were also producing dangerously low levels of serotonin. When the doctors added 5-hydroxytryptophan (5-HTP), a serotonin precursor, to their treatment regimen, Noah’s drooling and motor skill problems vanished and Alexis’s breathing went back to normal.

Alexis, now 14, was able to run track (and place in the top three) in her spring semester, and Noah played volleyball in this year’s Junior Olympics.

“For the first time, we based a medical management treatment on a molecular diagnosis that was established through genome sequencing...“This was no brilliant doctor, this was no new technology. This was a mom trying to figure out her child.”

http://the-scientist.com/2011/10/01/double-blind/