Friedreich ataxia (FA) is a progressive neuromuscular disorder of which there is no cure. It is inherited in an autosomal recessive manner, with the main genetic culprit being GAA triplet repeat expansion of both alleles of the Frataxin gene.
FA, while most often associated with ataxia, is in fact a multisystemic disease. Cardiomyopathy is a common clinical finding in many patients with FA, followed closely by diabetes mellitus. Because the effects of diabetes are so wide-ranging, it can aggravate many of the other symptoms of FA when uncontrolled.
Read more about FA etiology
How common is diabetes among individuals with FA? Studies suggest that up to 40% of patients, both children and adults, suffer from diabetes related to FA. Around half of the adult patient population have impaired glucose tolerance, a precursor to diabetes.
Diabetes is a common clinical condition; many children and adults in the community are diagnosed with it. Hence, there is a risk of complacency when diabetes is diagnosed in a patient with FA, since it can sometimes be viewed as a comorbidity that is not strictly related to FA.
However, studies indicate that patients with FA and diabetes have poorer functional status compared to patients with FA without this condition. Once again, this comes down to the fact that diabetes often worsens existing pathology and can too be considered a multisystemic disease.
“Despite the clinical relevance of FA-related [diabetes mellitus], no evidence-based clinical practice guidelines for screening or management currently exist,” Tamaroff and colleagues wrote in Diabetes Research and Clinical Practice.
This is because the mechanisms linking diabetes to FA are poorly understood. Studies have suggested that old age, longer GAA repeat lengths, and not being able to ambulate are key factors that predispose an individual with FA to diabetes, but not much more is known outside of that. Aggravating this lack of knowledge is the limited number of trials that focus on FA and diabetes.
Tamaroff and colleagues hence conducted a study in which they sought to understand the extent of the FA patient population that has diabetes, as well as how it is currently managed. They enrolled patients with a genetic diagnosis of FA, including 1104 participants (both children and adults) across 15 sites globally. Out of the 1104 participants, 96 having a confirmed diagnosis of diabetes.
The research team found that old age is a risk factor for developing type 2 diabetes mellitus among patients with FA (which is also the case among the general population). FA patients with diabetes are more likely to have severe disease, longer disease duration, and chronic stress.
In addition, the research team reported that cardiac disease was associated with an increased risk of FA-associated diabetes. These cardiac disorders include hypertrophic/dilated cardiomyopathy, as well as arrhythmias. This association is more pronounced in individuals with an FA age onset below 15 years of age.
Why is this the case?
“One possible explanation for the association between cardiomyopathy and FA-related [diabetes mellitus] is that individuals with severe FA are more likely to develop both comorbidities,” the study authors wrote. “Alternatively, [diabetes mellitus] may contribute to the pathogenesis of cardiac disease.”
The research team also reported that patients with both FA and diabetes are at significant risk of developing ketosis, a potentially life-threatening complication of diabetes. So what can be done to improve screening and care of FA patients at risk of developing diabetes? Certainly the best place to start is to improve screening services, although screening for some diseases (such as diabetes-related neuropathy) can be challenging at a local level. The next best thing is to ensure that family members of patients are screened where there is a clinical suspicion to do so, given the genetic component of FA.
The Importance of Working Together
While this article focuses on the link between FA and diabetes, clinicians who regularly treat patients with FA will know that a number of other pathologies are also linked to FA aside from ataxia, such as loss of coordination, sensory loss, visual dysfunction, and hearing difficulties.
FA differs from other neurodegenerative disorders such as Duchenne muscular dystrophy in that the manifestations of the disease are broader in range, meaning that morbidity is high. In light of the multisystemic damage that can occur in patients with FA, excellent teamwork between clinicians of different disciplines is key.
“FA frequently requires collaborative care among multiple specialists,” Lynch and colleagues wrote in the Journal of Multidisciplinary Healthcare. “Increasingly, such care exists mainly within centers of excellence for these disorders, where multidisciplinary care is a critical component and a necessity for getting the designation.”
Read more about FA treatment
Aside from diabetes, here are some other common complications of FA: neurological: ataxia and sensory/muscular dysfunction; cardiac: left ventricular hypertrophy and heart failure; orthopedic: scoliosis and pes cavus. Many patients also have mental health issues. In view of this, specialists of different disciplines need to work together in order to ensure that care is synced and that treatments prescribed are not overlapping in any way.
Oftentimes, multidisciplinary care works best when physicians find the time to gather together to have a brief discussion about a patient and their respective management plans. We must also not lose focus of the forest for the trees: the goal is always to ensure that patients with FA are fully supported and receiving the very best care possible.
“Excellent communication between specialists provides the essential element of high quality multidisciplinary care” will be necessary as “the need for integrated care in FA will continue to expand,” Lynch et al concluded.
References
Tamaroff J, DeDio A, Wade K, et al. Friedreich’s ataxia related diabetes: epidemiology and management practices. Diabetes Res Clin Pract. Published online March 14, 2022. doi:10.1016/j.diabres.2022.109828
Lynch DR, Schadt K, Kichula E, McCormack S, Lin KY. Friedreich ataxia: multidisciplinary clinical care. J Multidiscip Healthc. Published online June 28, 2021. doi:10.2147/JMDH.S292945
