Late-Onset Friedreich’s Ataxia May Be Confused with Another Genetic Disorder, Case Study Finds

Symptoms of late-onset Friedreich’s ataxia may be confused with those of another genetic disorder, Charcot–Marie–Tooth (CMT) disease, according to a case study.

Researchers called for a careful evaluation of patients to prevent misdiagnosis.

The study, “Late-Onset Friedreich’s Ataxia (LOFA) Mimicking Charcot–Marie–Tooth Disease Type 2: What Is Similar And What Is Different?,” dealt with a man who was thought to have CMT but who actually had Friedreich’s ataxia. The research was published in the journal Cerebellum.

Charcot–Marie–Tooth  disease, the world’s most common hereditary nerve disorder, shares several manifestations with Friedreich’s ataxia. Four are nerve malfunction, abnormal curvature of the spine (kyphoscoliosis), abnormal foot shape (pes cavus), and distal limb atrophy, or weak arm and leg muscles. Other shared symptoms include loss of reflex function — the ability of muscles to contract in response to being struck; proprioceptive loss, or the body’s inability to retain a position in space; and sensory gait ataxia, or loss of movement coordination.

The 32-year-old man in the study had increased difficulty walking in the previous four years. The weakness in his lower limbs also led to frequent falls, he said.

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Neurological examination revealed he had nerve malfunction, muscle atrophy, abnormal foot shape, loss of reflex function, an inability to retain a position in space, and steppage gait, or an inability to bend his ankle while walking. Although these symptoms suggested CMT, the man also had two symptoms that suggested Friedreich’s ataxia: severe scoliosis, or curvature of the spine, and square wave jerks, or abnormal eye movements.

Doctors decided to test him for mutations in the GAA gene, which encodes frataxin, the protein involved in Friedreich’s ataxia. They found 66 repeats in the gene, indicating that the man had Friedreich’s ataxia and not CMT. Unlike most Friedreich’s ataxia patients, who develop the disease in childhood, he developed it later.

“[T]his case reinforces that other genetic conditions may clinically resemble CMT,” researchers wrote. “The clinical similarities between CMT and FRDA include a symmetrical neuropathy axonal in [Friedreich’s ataxia]), steppage gait, and eventually scoliosis. We suggest that late-onset forms of hereditary neuropathies should be carefully evaluated, since [later onset of Friedreich’s ataxia] may be a CMT mimicker.”

Friedreich’s ataxia is an incurable neurodegenerative disease. It stems from a defective frataxin protein caused by repeats of a DNA sequence. The repeats, which scientists dub GAA repeat expansion, impair the normal expression of the protein.

By reducing frataxin levels, the repeats cause several problems at the cell level.

Low levels of frataxin are responsible for muscle weakness, loss of muscle coordination, abnormal sensitivity in the limbs, alterations in the structure of some brain regions — such as the cerebellum — and decreased life expectancy.