When Babies Don’t Cry: Doctors Discover New Genetic Disorder That Affects Children's Eyes, Muscles, And Liver
After a long search for answers, a group of parents and scientists have discovered a new genetic disorder. There are currently only 14 known human beings with this newly-defined condition, characterized by a rare gene mutation that makes a child unable to shed tears. It’s known as NGLY1 deficiency.
A Stanford School of Medicine news release notes that the discovery was “unusually fast” due to a combination of “modern gene-sequencing techniques, social media and old-fashioned detective work.”
According to a CNN report about a girl named Grace Wilsey, the condition, unknown at the time, caused lethargy and unfocused eyes as well as muscular problems in the young child. Grace Wilsey’s parents knew there was something wrong with her since a young age; she was unable to eat much, and had been taken to countless doctors and hospitals, with no one able to make a diagnosis. It was the fact that Wilsey’s parents were able to connect with other people who had the deficiency that ultimately gave scientists the chance to define the disease by comparing several cases.
Wilsey had high levels of AST and ALT liver enzymes, which were a sign of liver damage — but doctors couldn’t figure out the underlying problem. On top of that, Wilsey had developed hypotonia, a condition that made her physically limp. She also had developmental problems in cognition. After taking their daughter to hundreds of doctors, her father Matt Wilsey found Matthew Bainbridge at Baylor College of Medicine in Texas, who was a doctorate student in structural and computational biology and molecular biophysics at the Human Genome Sequencing Center.
Bainbridge first crossed known disorders off the list. “Your first instinct shouldn’t be ‘I’m going to find something new’ when trying to figure out a mysterious condition, Brainbridge told CNN. “[It should be] ‘I’m going to find something someone has already discovered.’” Bainbridge discovered that there was something wrong with Wilsey’s NGLY1 gene, then continued researching that particular gene for more answers.
He ended up coming across a blog written by Matthew Might, a man who had a son with this mutated NGLY1 gene. Might referred to his son as “Patient 0,” or the only known human to have this new genetic disorder. The NGLY1 gene had two different mutations, and had symptoms similar to Grace’s — especially the fact that neither of these children were able to cry.
Might and the Wilseys connected, and soon scientists were working on finding others with the same condition. “I think cognitively it’s really nice to have a label,” Kristen Wilsey told CNN. “Once you do have a name, you can then start looking for a cure.” Currently, the amount of people known with the disorder is up to fourteen, and there are now five different treatments being studied and developed.
“This represents a complete change in the way we’re going about clinical medicine,” Gregory Enns, an author of the paper and a geneticist at Lucile Packard Children’s Hospital Stanford, told CNN. “This is happening so quickly because… so many people are coming at this from so many angles.”
However, plenty of work remains to be done to understand NGLY1 deficiency. Teams of researchers are examining different models of the disease in mice, fruit flies and stem cells, in order to understand how the gene is linked to the symptoms, and how this information could produce treatments.
“In order to diagnose patients, we must admit the limitations of our medical knowledge,” Matt Wilsey and Matthew Might wrote in an editorial with the journal paper. “Sometimes the best ideas come from individuals ‘outside the box’ (i.e. patients and parents)… Sometimes the least likely gene candidate is the answer.”