This 24-year-old woman dates the onset of her problems to about 6 years ago, when she first noted balance problems, with progressive difficulty walking straight but no falls. Physical therapy exercises were helpful, though stress at college made symptoms worse. More recently, she noted that her eyes tended to jerk away when trying to focus and her speech was hesitant and slowed. Of note, when she closes her eyes, she may feel transiently imbalanced (one of her early symptoms was to hold on to the shower wall when showering because she would perceive a tendency to fall when closing her eyes while shampooing). At the age of 11 years (sixth grade), she developed progressively worsening scoliosis, which was treated with spinal fusion at the age of 14. She had normal developmental milestones and had been a straight-A student.

Our patient had ataxia with scoliosis of onset in early teens, associated with areflexia and mild Romberg sign in the absence of cognitive impairment. These findings were most consistent with Friedreich ataxia, supported by atrophy of the cervical cord on MRI and confirmed by an expansion in the frataxin gene in both alleles (956 and 433 repeats). Despite the magnitude of the repeat expansion, there was no measurable proprioceptive impairment (except indirectly
through a mild Romberg sign) and no cardiovascular or glycemic control symptoms, though periodic monitoring for these disease-associated complications was warranted.

The diagnosis of Friedreich ataxia (FRDA), in its classic form, requires the onset of ataxia or scoliosis before age 20, along with rapid subsequent appearance of areflexia, extensor plantar response, position and vibration loss, and other skeletal deformities (pes cavus), in the absence of ophthalmoplegia and dementia. Pes cavus or scoliosis in parents should suggest an autosomal dominant ataxia, such as Charcot-Marie-Tooth (CMT). The ataxia of FRDA is, however, more sensory than cerebellar and should be included in the differential diagnosis of other sensory ataxias, such as vitamin E deficiency, vitamin B₁₂ deficiency, and nitrous oxide myeloneuropathy (Table 69.1).

FRDA is caused by an unstable GAA repeat within the first intron of the frataxin (FXN) gene on chromosome 9q13. Affected persons have from 81 to over 1,000 repeats in both their alleles (homozygous expansion). When the expansion is heterozygous, the other allele must have a point mutation. Hypertrophic cardiomyopathy and diabetes mellitus develop when
GAA repeats exceed 500. Brain MRI shows atrophy of the upper cervical cord with nearly normal cerebellum (Fig. 69.1). Another ataxic disorder characterized by cervical cord atrophy is adult-onset Alexander disease, whereby palatal tremor is often part of the clinical picture.