Wolfram and a deviceMarch 7, 2019
A 25-year-old male patient presented with repeated episodes of loss of consciousness and seizures. These episodes were associated with hypoglycemic events, especially at night. The patient and his family were extremely worried and consulted with Dr Arun Menon, Endocrinologist, Amrita Institute of Medical Sciences, Kochi. The patient had type 1 diabetes since childhood, progressive deafness, and was visually impaired. He had been previously diagnosed with Wolfram syndrome type 1.
Wolfram syndrome is characterized by juvenile onset diabetes mellitus and optic atrophy. It is primarily an autosomal recessive inherited disorder that affects 1 out of 100,000 to 1 out of 770,000 individuals worldwide. Because of the associated neurodegenerative presentation, it is also referred to by the acronym, DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Often, a variety of other symptoms may also be associated, such as ataxia, seizures, depression, gastrointestinal problems, sleep conditions, autonomic neuropathy etc..
Depending on the genetic mutation, Wolfram syndrome can be type 1, caused due to mutations in the WFS1 gene, or type 2, caused due to mutations in the WFS2 or CISD2 gene. WFS1 gene encodes for the protein wolframin, which plays a role in protein folding by regulating calcium levels in the endoplasmic reticulum of cells. In the pancreas, it is specifically important for folding of the proinsulin protein. In the inner ear, it is required for maintaining calcium levels essential for hearing. Mutations in wolframin result in improper functioning of the endoplasmic reticulum, and consequently, cell death. Prominently, insulin-producing beta cells are affected, which results in diabetes mellitus; and a gradual loss of the cells and the optical nerve eventually results in blindness. Cell death in other organs may cause a variety of other signs and symptoms associated with Wolfram syndrome.
Currently, there is no cure for this syndrome and long-term prognosis is completely dependent on the affected organs. Several therapeutic options, including drugs that can balance calcium levels in the ER or improve protein folding and trafficking in the ER, and stem cell therapy to regenerate the destroyed cells are being explored. However, as of now, treatment is only supportive and based on the symptoms in each individual. Most individuals with Wolfram syndrome have an average lifespan of only 30-40 years.
The patient and his parents were extremely worried because of the nocturnal hypos which significantly affected their quality of life. The patient was already being treated with multiple daily injections of insulin. However, this treatment was not effective and resulted in unpredictable episodes of hyperglycemia and hypoglycemic without any recognizable warning signs. The patient was consequently afraid of taking the insulin as the effect was unpredictable and even small doses could result in dangerous hypos. To provide a more continuous treatment strategy, Dr Menon started him on an insulin pump. The continuous subcutaneous insulin infusion (CSII) allows for constant, continuous infusion of insulin under the skin. The insulin pump was effective in immediately stabilising the glucose levels. However, a major concern was whether the patient would be able to manage the pump with his visual and hearing impairment. Surprisingly, the patient adapted exceptionally well and managed to regularize his life style as well as his glucose levels with the help of the pump. This HbA1c levels improved from 13% to 8.2% between June 2017 to February 2018.
To ensure appropriate glucose monitoring in addition to insulin delivery, the patient was started on a continuous glucose monitoring system. This is a cell phone app based real-time glucose monitoring system that provides continuous interstitial glucose profiles directly on the cell phone. This system sends regular alerts on the cell phones based app, effectively preventing hyperglycemic or hypoglycemic episodes and allowing for even better glucose level control. Other benefits of using such a continuous monitoring system include a reduction in checking interstitial glucose to twice a day only, and that too only for calibration purposes. As of September 2018, the patients HbA1c levels were at 7.3%. While these are still higher than normal, they are much improved compared to a year ago, and the patient is able to manage his glucose levels much more effectively and is witnessing far fewer hypoglycemic episodes.
While diabetes and related conditions are dramatically increasing worldwide, technology is also advancing by leaps and bounds. Several monitoring and drug delivery devices are available now, even as others are in the pipeline, to make it simpler to control diabetes and continue retaining good quality of life. Dr Menon is optimistic for the future: “With the technological advances, it is now possible to get real-time glucose profiles for a better understanding of how glucose levels fluctuate in each individual, and treatment should be tailored accordingly.”