Doctors at the Hadassah-University Medical Center in Jerusalem and colleagues in Germany and Switzerland have identified consistent symptoms of progressive blindness in three Israeli patient families. The disease was discovered in lab mice but had not been seen in any patients until now.The sequencing of the human genome has made it possible for today’s scientists to discover potential disorders for which there have previously been no known human victims. Now that the cause of symptoms is known, it is possible to think about enzyme-replacement therapy.The international team that worked on the discovery included Prof. Eyal Banin, Dr. Samer Khateb and Dr. Menachem Gross, along with others at Hadassah, and Tamar Ben-Yosef of Haifa’s Technion-Israel Institute of Technology, and a group headed by Prof. Thomas Dierks of Bielefeld University in Germany.The disorder is called MPS III-E – originally named “Dierks’s disorder,” after its discoverer. Genome analyses at Switzerland’s University of Lausanne had delivered a candidate gene on which Dierks published a research article in 2012.However, it took until now to find that Israeli patients indeed suffer from the disorder. The team has now presented its analysis of the disorder in the journal Genetics in Medicine, published by the Nature Publishing Group.The researchers were surprised in April to first hear about the Israeli patients, who did not start to show the symptoms before the age of 40. “Based on our studies with mice, we assumed that the symptoms would emerge much earlier, perhaps after 10 years,” said Dierks. His explanation for the delay was, “Large parts of the heparan sulfate molecule can be degraded without arylsulfatase G. Therefore, it takes more time to accumulate.”Through biochemical studies and genetic analyses, it was finally possible to confirm the disorder in five patients from the Israeli families. “These persons have increasingly poor vision due to progressive retinal atrophy. They also develop an inner-ear hearing impairment,” said Dierks. “These are the same symptoms, alongside others, that we also found among mice in our earlier studies.”Bielefeld scientists had studied the disorder in mice, switching off the gene responsible for producing the enzyme arylsulfatase G. This ensured that the carbohydrate heparan sulfate could no longer be fully degraded. As a result, the carbohydrate accumulated in the cells, explained Dierks. This accumulation takes place in the lysosomes, the “recycling plants” of the cells. Due to this metabolic dysfunction, the breakdown also of other substances such as lipids and proteins gradually comes to a standstill. The accumulation then increases the size of the lysosome until it destroys the cellM and that brings about the disorder.Dierks wrote that the required enzyme could be produced with the help of cell cultures and injected intravenously. Once it is carried through the body via the blood, it would break the heparan sulfate in the tissues. “However, the brain is hard for the enzyme to reach due to the blood-brain barrier,” said Dierks.“Moreover, the disorder has to be diagnosed through gene tests before the symptoms appear, if treatment is to commence before damage has become irreparable.” Now that the symptoms resulting from this hereditary disorder in humans are known, Dierks expects that the genetic defect will be diagnosed in more people.