The vast majority of patients with Friedreich’s ataxia develop symptoms in the first or second decade of life, enabling an early diagnosis and early medical attention to alleviate symptoms of the disease. However, a small number of patients develop late-onset Friedreich’s ataxia (LOFA) between the ages of 25 and 40, and an even smaller number develop very late-onset Friedreich’s ataxia (VLOFA). Patients who develop LOFA or VLOFA tend to have milder disease progression, but clinical manifestations are no less variable in adult-onset Friedreich’s ataxia as they are in childhood-onset Friedreich’s ataxia.
One case in particular highlights the variety of clinical manifestations of VLOFA. A 64-year woman presented at the clinic with slowly progressive dystonia, or an impaired ability to vocalize sounds from the vocal organs. Before that time, in her mid-40’s, she experienced balance and gait disturbances.
Further lab testing identified that she had trouble speaking clearly, responding to deep tendon reflexes, and coordinating her hand-eye movements. Her vocal impairment was of special consideration to clinicians, as only a few previous cases of mitochondrial myopathies have reported laryngeal dystonia. “Presence of laryngeal dystonia in a patient with an ataxic syndrome should lead physicians to consider Friedreich’s ataxia in the differential diagnosis,” wrote Dr. Silvia Rota, lead author on the study “Very Late-Onset Friedreich Ataxia with Laryngeal Dystonia,” published in Case Reports in Neurology.
To pinpoint the cause of this patient’s symptoms, her clinicians conducted a molecular genetics analysis, and they discovered mutations in the gene encoding the protein frataxin (FXN). The mutations, called 210- and 230-trinucleotide GAA repeat expansions, were relatively small compared to some FXN mutations. Indeed, patients who develop LOFA or VLOFA tend to have smaller GAA repeats (<500), with VLOFA patients typically showing fewer than 300 in at least one expanded allele. “Our case is one of the rare cases of VLOFA having <300 repeats in both alleles, and represents the first description of abductor laryngeal dystonia in Friedreich’s ataxia,” noted the authors.
Case reports such as these are important to defining the range of symptoms and clinical manifestations of Friedreich’s ataxia. When researchers establish patterns of cause-and-effect behavior, as in the case of <300 GAA repeats associated with VLOFA, it becomes easier to pinpoint the cause of disease and helps suggest treatments that may be most effective at addressing symptoms.