One family’s tale: “Within hours of his birth, it was clear he had problems,” recalls a mother who later learned her son was born with a metabolic disease. First, he could not eat; then he could not breathe; and then he went into convulsions. Despite extensive testing, the United States physicians where the couple lived were unable to diagnose his disease and the child died 16 months later.
The grieving parents were told that the problem was genetic and that there was a one in four chance that any future children they had would be affected. Fortunately, their third child, like their first, was born healthy. But their fourth child, born after the couple moved to Israel, was not. The parents, deciding to care for the child themselves, took their sick son home. Seven weeks later, they found the baby dead in his crib. It was at this point that the distraught couple sought counseling with Prof. Orly Elpeleg, Director of Hadassah’s Center for Metabolic Diseases.
In order to find some answers, Prof. Elpeleg, an internationally known expert in metabolic diseases, suggested that they examine the DNA of all four children born to this couple. Even though the first child had died in the United States, the beauty of science today, explains Prof. Elpeleg, is that the DNA could be brought to Jerusalem by Prof. Ed Kolodny who had cared for the child in New York but, unfortunately, was unable at the time to reach a diagnosis. The fourths child’s DNA was obtained through a skin biopsy and the subsequent culturing of the cells.
“We found two areas of the children’s DNA that were identical in the dead children and differed from the same area in the healthy children,” Prof. Elpeleg explains, “and could, therefore, be involved in causing the sickness.” But because they didn’t know which of the two it was, she said, “we couldn’t offer a diagnosis or prenatal testing.”
When the mother delivered her fifth child, Hadassah’s pediatric neurologists examined her and found the child to be normal. But three weeks later, the parents were back at Hadassah. The little girl had stopped breathing. She was ventilated, intubated, and stabilized—but she remained metabolically ill.
The tragedy for this baby and her family, however, has proven to be science’s gain. Prof. Elpeleg describes the process:
“We examined the baby’s DNA and found it contained only one of the two moot areas that we’d pinpointed in her siblings. We now had our culprit gene.”
Not only did the Hadassah researchers pinpoint the gene responsible for the child’s illness and identify a gene new to science, but they also discovered that it mutated in a way never seen before in human beings. This means that a new mechanism of causing disease has been identified. Prof. Elpeleg explains: “The mitochondria, which is the energy production part of cells, has to synthesize a small, but essential, number of its own components. For that purpose, the mitochondria has to replicate, transcribe, and translate the genes, encoding these components. We identified a defect in one of the 22 enzymes which charge the translation tools. This is the first time a defect in one of the mitochondrial chargers has been identified in a human being.”
“We’re hurrying to check our other patients to see if this new mechanism is found in other mutated genes,” says Prof. Elpeleg. “We’re confident that the knowledge we’re accumulating will eventually lead to cures for devastating genetic illnesses.”