Despite the constant evolution of medical science, an increasing number of medical mysteries have yet to be solved. What is more intriguing is that the key to these medical puzzles often lie in some of the daily routines of our lives.
One such case was reported in a recent issue of the journal Genetics in Medicine, in a study led by Dr. Gregory M. Enns, MB, ChB and pediatric geneticist at the Lucile Packard Children’s Hospital, Stanford, and Dr. Matthew Bainbridge, PhD, a postdoctoral associate at the Baylor College of Medicine in Houston, Texas.
The subject of the report was Grace Wilsey, daughter of Matt and Kristen Wilsey, who, along with developmental abnormalities, hepatic, and neurological problems, presented with a very peculiar trait — she did not produce tears while crying, though her eyes became moist. This became even more alarming when it was found that her symptoms did not match with any known possible disease or condition.
Dr. Enns, who was Grace’s doctor at the hospital where she was being treated, along with his team of attending physicians, investigated the symptoms closely and were compelled to analyze Grace’s genotypic data, as phenotypical analysis bore no results. On comparing Grace’s genome to a normal control, several mutations were brought to light. After intense analysis, researchers zeroed in on a mutation in the NGLY-1 gene as the probable culprit. NGLY-1 encoded for the enzyme N-Glyconase -1, a “housekeeping” enzyme responsible for some of the vital functions of our body.
Dr. Enns’s conclusion was supported by Dr. Mathew Bainbridge’s findings when he worked on the same case when approached by Kristen and Matt. The latter had earlier worked on another child’s problems at Duke university that were somewhat similar to Grace’s, but could not determine anything conclusive due to lack of a proper reference. On comparing Dr. Enns’s data for Grace’s symptoms and comparing the child’s data as well, it was concluded that the mutation in NGLY-1 was the causative factor. The strongest link to these two cases was the fact that both did not produce tears when crying.
Scientifically speaking, the enzyme N-Glycanase is responsible for the translocation of misfolded r — incorrectly folded proteins — to the cytosol to be digested by the proteosomes. Mutations in this gene causes the proteins to accumulate within, which lead to an array of functional abnormalities, depending on the severity of the mutations. It was something never studied before, and was concluded to be a novel autosomal disorder.
Though the mutation was identified, its varied severity leaves much to be researched upon in the future. So far, there have been 8 such cases where mutation in the NGLY-1 was identified, with 6 of them having severe manifestations, and the remaining 2, including Grace, have had only minor symptoms comparatively.
It is also important to note that, apart from the medical significance of this issue, the physical and emotional condition of the patient is also very crucial. It is a matter of great emotional turmoil for parents who deal with such a situation. According to Matt Wilsey, “before we had a diagnosis, we always had the fear of the bottom dropping out.” Without knowing exactly what was wrong, he and his wife constantly worried that Grace might suddenly deteriorate. “In that situation, you’re always on the defensive; you can’t enjoy parenthood.” To this, Kristen added, “With a diagnosis, we can start working on a cure or a way to alleviate some of Grace’s symptoms. It’s hard to describe that feeling. When we got the news, we were so excited that neither of us could sleep.”
A more human aspect was added to this study by including the fathers of the victims as co-authors, to contribute their opinion for parents in similar situations. Matt and another child’s father were co-authors of this study as well.
Science has taken yet another euphoric step ahead with this study. According to Dr. Enns, “We are likely detecting the most severe form of NGLY1 deficiency – ascertainment bias – and it is quite possible that more mild forms of the disease exist.”