Common comorbidities and their management in Friedreich’s ataxia

Last updated March 4, 2024, by Lindsey Shapiro, PhD
Medically reviewed by David Lynch, MD, PhD

While mainly characterized by its neurological manifestations, Friedreich’s ataxia (FA) is a multisystemic disease that may affect a range of bodily processes, leading to comorbidities such as cardiac disease, diabetes, difficulties with urination, and mental health challenges.

While such comorbidities may not be evident at the time of diagnosis, they commonly develop as FA progresses. Patients with late-onset disease are less likely to experience the non-neurological comorbidities of FA relative to patients with a typical onset.

Heart issues

Cardiac involvement affects nearly all FA patients to at least some degree at some point, and is the leading cause of early death in this patient population. Hypertrophic cardiomyopathy is the most common manifestation. Systolic dysfunction and complications such as arrhythmias and heart failure often emerge as the disease progresses and contribute to an increased mortality risk.

Standard guidelines from the American Heart Association and American College of Cardiology may generally be used for cardiac management in FA.

Diabetes

About 8%-32% of FA patients may have diabetes, with others showing signs of glucose intolerance.

Diabetes in children with FA typically reflects non-autoimmune loss of pancreatic Beta cells and presents with difficulties from relative lack of insulin. Such presentation can include the classic diabetes triad of urinating too much, drinking too much, and eating too much, but usually the presentation is more subacute. Patients can simply feel ill without specific diabetic symptoms or note a change in some of the other features of FA.

Still, some individuals can present with diabetic ketoacidosis, a state of severe dehydration with very high blood sugars.

In adults, the onset of diabetes may be even more gradual, with slowly evolving insulin deficiency and resistance associated with beta cell dysfunction. Still, as diabetes in adults with FA includes both lack of insulin and increased insulin resistance, individuals in their 20s can present with fulminant diabetic symptomatology or even ketoacidosis.

Evaluation

Establishing a diabetes diagnosis in FA is similar to the general population:

• Hemoglobin A1c (HbA1c) equal or higher than 6.5%
• Fasting plasma glucose equal or higher than 126 mg/dL
• Oral glucose tolerance test: two-hour glucose equal or higher than 200 mg/dL
• Random glucose equal or higher than 200 mg/dL in patients with symptoms of hyperglycemia.

Management

For all children and adults with evidence of decreased insulin secretion, insulin is recommended as the primary treatment of FA-associated diabetes. In adults with evidence of insulin resistance, an individualized application of current guidelines for type 2 diabetes is recommended, with consideration of other comorbidities in FA.

Glucose lowering medications may be used, although there is no specific clinical evidence on their use in FA patients; a full review of associated risks should be taken before prescribing these medications.

Non-insulin treatments may include:

• Metformin
• Sulfonylureas
• Thiazolidinediones
• Glucagon-like peptide-1 agonists
• Sodium-glucose cotransport 2 inhibitors.

Bladder issues

Lower urinary tract (LUT) symptoms are prevalent in FA, with overactive bladder (urgency and, rarely, true incontinence) being the most common presentation due to involuntary and unpredictable contractions of the bladder’s detrusor muscle. The risk of upper urinary tract damage in FA is low.

Evaluation

Conditions to rule out before initiating treatment:

• Urinary tract infections (UTI): These may mimic overactive bladder symptoms and worsen neurological manifestations.
• Urological/gynecological causes such as prostate enlargement or stress incontinence.

Voiding dysfunction and incomplete bladder emptying are not common in FA. Prior to initiating treatment, an assessment of post micturition residual urine should be performed using ultrasound or in-out catheterization.

Urodynamic studies are not routinely performed except in cases where LUT symptoms are refractory to treatment or intravesical treatment is planned.

Management

Typical management of LUT symptoms include:

• Lifestyle changes: Patients should be advised to cut down intake of caffeine, fizzy beverages, and alcohol, and informed about timed voiding and bladder retraining where appropriate. Fluid intake should be determined on an individual basis.
• Antimuscarinic medications: These are required for most FA patients with overactive bladder. Artificial saliva may be concurrently prescribed if dry mouth side effects of these medications are intolerable.

If patients are refractory to standard treatment, other options include:

• Beta-3 receptor agonists such as mirabegron
• Percutaneous tibial nerve stimulation
• Intradetrusor injections of botulinum toxin A.

In patients found to have persistently elevated post-void residual volumes exceeding 100 mL, clean intermittent self-catheterization (CISC) is indicated. An indwelling catheter may be required in those with advanced disease.

Referral to a urologist is indicated in cases of hematuria, suspicion of a concomitant urological condition such as prostatic enlargement, cases of frequent UTIs, or when symptoms are refractory to medical management. Referrals should also be made when considering botulinum A treatment or suprapubic catheter insertion.

Mental health issues

Although not presenting or diagnostic symptoms of FA, mood disorders such as anxiety and depression are commonly experienced in the FA population, and thus, patients should be routinely screened.

If depression or other mental health issues are suspected, patients should be treated with standard interventions used in the general population, including counseling or medications where appropriate. Lifestyle changes, such as exercise, diet, and social engagement, may also have a positive impact.

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