Emory Report
April 27, 2009
Volume 61, Number 29


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April 27
, 2009
Neurologist works to solve rare disease's puzzle

By Quinn Eastman

Neurologist H. A. “Buz” Jinnah has devoted a large part of his career to studying the peculiar puzzle behind Lesch-Nyhan disease.

Young men and boys with this inherited disorder experience uncontrollable urges to bite themselves, slam their arms into doorways and otherwise harm themselves. How a mutation in one gene can lead to such specific and self-destructive behavior is still mysterious.

Jinnah, who came to Emory at the beginning of 2009 from Johns Hopkins, is well-placed to provide some answers. He trained at UC San Diego with William Nyhan, the pediatrician who identified the disease in the 1960s, and sees patients with the disease from across the country.

Jinnah says that what Lesch-Nyhan patients exhibit is at the far end of a spectrum of self-injurious behaviors many people practice, ranging from relatively innocuous nail- or cuticle-biting to more problematic bulimia.

In recent lectures, Jinnah has shown a video recording of a Lesch-Nyhan patient in a wheelchair. During the video, Jinnah removes a strap that restrains the boy’s arm. In a few seconds, the boy’s hand is drawn into his mouth, as if attracted by a magnet, and Jinnah has to react quickly to stop it.

“Some of these guys can tell you that these feelings are coming,” he says. “They can go for a while without their restraints, but they will ask you to have the restraints put back on.”

Lesch-Nyhan patients tend to make stiff movements and are often unable to walk. They can be seen as cognitively impaired because they have problems concentrating.

At the same time, they are keenly aware of what’s happening around them and shouldn’t be treated like wallpaper, Jinnah says. He recalls a conference where doctors could learn about the disease by asking questions of patients. At the end of the session, one boy asked permission to ask the doctors a question.“Why do doctors and nurses sometimes talk about us like we’re not here?” he asked.

The disease comes from mutations in a gene on the X chromosome called HPRT. Boys are vulnerable to the disease because they have only one X chromosome. The gene encodes an enzyme that recycles building blocks of DNA called purines. Without the enzyme, the building blocks are broken down into uric acid, which accumulates in the body and can cause painful swelling of the joints.

These gout-like symptoms can be treated with medication, but the neurological problems and striking behavior don’t go away. Not all boys with mutations in the HPRT gene exhibit self-injurious behavior, but the more severe the mutation and disease, the more likely those symptoms are to appear.

Less than a thousand cases of Lesch-Nyhan exist in the United States. Jinnah is sometimes asked about the utility of researching such a rare disease.

He likes to quote 17th century medical pioneer William Harvey, who wrote:

“Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path.”

It appears that overabundant purines also perturb the development of certain parts of the brain. Studying Lesch-Nyhan can shed light on how brain development is controlled. Lesch-Nyhan disease even has some connections with Parkinson’s disease, and in some ways is a mirror image of Parkinson’s.

Lesch-Nyhan patients have a deficiency of cells that make the chemical messenger dopamine in the basal ganglia, the same part of the brain affected by Parkinson’s disease. Jinnah has been investigating how electrical stimulation of the basal ganglia, used to help people with Parkinson’s regain some mobility, can also help Lesch-Nyhan patients control their rebellious impulses.

He works closely with his wife, Ellen Hess, who arrived at Emory at the same time. She specializes in basic research on the movement disorder dystonia, characterized by tense muscles and twisted limbs, and uses mouse models to identify potential treatments.

“We started out with separate labs, but we’d help each other with everything and sometimes reagents or people would be shared,” he says. “Merging our operations actually made things less confusing.”

Friends and colleagues refer to Jinnah as “Buz,” a nickname bestowed by his older sister when they were children.