Czech scientists find cause of disease

It's a hereditary disease that hits people in the prime of their lives. Those afflicted can live a relatively normal existence until their 30s, when they may suddenly begin experiencing psychological problems like depression and bipolar disorder. Many are prescribed antidepressants. Within two years, the psychological disorders manifest into spasms and seizures, and eventually the person succumbs to mobility disorders, paralysis and even dementia.

The condition, known as Kufs disease, worsens with time, and affected individuals usually survive about 10 years after the first symptoms.

"A person can live a normal life, have children, go to work and see no signs until they hit their 30s. That's when Kufs disease first affects the individual," said Stanislav Kmoch, doctor and head researcher at the Institute of Hereditary Metabolic Disorders (ÚDMP) in Prague. "Once the first symptoms appear, it's a rapid progression where people lose all neuro-cognitive abilities, consciousness and, within five to six years, can become a vegetable and eventually die."

On Sept.19, a team of Czech researchers from ÚDMP of the First Medical Faculty of Charles University in Prague announced they had uncovered the cause of this late-onset disease: the DNAJC5 mutated gene.

Kufs is a rare disease that is part of a group of genetic disorders called neuronal ceroid lipofuscinoses (NCL). It is a condition that primarily affects the nervous system, causing progressive problems with movement and thought. According to research published by the U.S. Library of Medicine, NCLs, as a group, affect two to four per 100,000 newborns worldwide. It is estimated that Kufs disease represents 1.3 percent to 10 percent of all NCL cases. Since the disease is hereditary, Kmoch said, there is a 50 percent chance of a person getting the mutated gene if one of his or her parents had Kufs. Once people have the mutation, he said, there is a 100 percent chance they will get Kufs disease.

"Because it is inherited, all of those who are affected by [the age of] 30 know what the disease looks like because they had parents who were affected by the same disease," Kmoch said. "Knowing your pedigree and family background helps people understand this is not just depression when they first get the symptoms."

For years, the genetic cause of the incurable brain disease was unknown, until the late professor Milan Elleder found a Czech family 10 years ago that had the symptoms. Elleder and other researchers were able to study this family and their extended family through genetic mapping and linkage.

From the information gained from this individual family, combined with scientific research and analysis from scientists and researchers around the world, Kmoch and a team of 15 scientist started on the path to find the genetic mutation that causes Kufs. ÚDMP's project started three years ago and was funded by the Education Ministry with two rounds of institutional support for research, not grants. In 2010, they discovered the mutation in the gene, and it took another year to prove the causality of Kufs.

"We identified the Kufs disease gene in this Czech family, and then we studied 20 other families and identified another five having mutations in this specific gene, DNAJC5," Kmoch said. "This means that many more were probably affected because they had children and extended family. It's like a ripple effect."

Unfortunately, Kmoch said, finding the cause does not equate to finding the cure.

"If you identify the cause of a genetic disease, it's not the end. It's the beginning of the end," he said.

Right now, ÚDMP researchers are starting to understand the disease and are studying the mechanisms that start the mutations in the gene and leads to more effects, like how human neurons deal with these mutant proteins.

"Many people underestimate the research of rare diseases," Kmoch said. "Mother nature is showing us what happens to humans if just one of the genes is not acting properly."

Since the news of the findings, a number of people in their 30s have already contacted ÚDMP to report that they are noticing some of the beginning symptoms. Kmoch said people can contact the researchers and receive feedback right away. If people suspect they may have Kufs symptoms, they need to have a family history ready in order to discuss whether it fits into the criteria of Kufs, Kmoch said. If it does, they can sequence the gene and see if they carry the DNAJC5 mutation within a couple of hours. Either a neurologist or the team at ÚDMP would be able to analyze this, he said.

"General physicians, I dare to say, are not [as] aware of all the genetic disorders - there are more than 9,000 and less than half have a known cause," Kmoch said. "While there might not be treatment yet, it's still important to understand the disease since it can be passed down."

Megan Battista can be reached at
features@praguepost.com