Vision and balance disturbances initially blamed on aging

Ms. V, a physically fit 55-year-old white woman noticed progressive visual disturbance, specifically decreased near-visual acuity and difficulty distinguishing colors. She noted that her handwriting was getting increasingly illegible, she was making frequent typing mistakes, and she was unable to see yellow highlighter. Three years earlier, her optometrist expressed concern that he could not correct her vision to 20/20 with eyeglasses.

Ms. V had also noted that her balance was getting worse. Friends joked that if they didn’t know better, they’d think she had been drinking on the job. When she did consume alcohol, she began slurring her words after one drink. Ms. V had started touching walls while walking and had to use handrails to go up and down stairs.

Routine blood work was within normal limits. The patient’s primary-care provider told her that she was just getting older. Ms. V remembered that her mother had balance problems in her 50s and used the word “ataxia,” but was undiagnosed. Her mother also developed macular degeneration in her 70s. The family history was positive for early-onset ataxia in the maternal brother’s child. After three years of symptoms, Ms. V was referred to a neurologist.

1. Background

Genetic testing revealed that Ms. V was positive for spinocerebellar ataxia type 7 (SCA7). Recognizing SCA7 can be difficult, as the condition’s early symptoms can mimic other disorders, including heavy-metal intoxication, vitamin D deficiency, multiple sclerosis, and diabetic retinopathy. SCA7 is also known as autosomal dominant cerebellar ataxia type 2 or ataxia with pigmentary retinopathy. SCA7 is one type of ataxia among a group of inherited diseases of the central nervous system. As in other inherited ataxias, SCA7 is the result of genetic defects that lead to impairment of specific nerve fibers carrying messages to and from the brain. These defects cause degeneration of the cerebellum.¹

2. Diagnosis

Diagnosis can be made based on family history of SCA7 and/or symptoms of SCA7 in a sibling or close relative and cerebellar ataxia with progressive incoordination, symptoms of dysarthria/dysphagia, dysmetria, and dysdiadochokinesia. SCA7 patients also have cone-rod retinal dystrophy (demonstrated by abnormal electroretinogram), blue/yellow defect on color vision testing, and—later in the disease—macular degeneration. Molecular genetic testing will show abnormal alleles in gene ATXN7. This is the only gene known to be associated with SCA7.²

Autosomal dominant inherited spinocerebellar ataxias like SCA7 have a gene mutation that causes nucleotide bases (cytosine, adenine, and guanine [CAG]) to form a sequence that is repeated many times.³ These unstable stretches favor expansion of the polyglutamine tail. The greater the number of repeats, the longer the tail, and the longer the tail the greater the neuronal injury secondary to proteolytic cleavage and nuclear accumulation of toxic products.⁴ When the number of CAG repeats expands beyond the normal range, the patient becomes symptomatic. The number of CAG repeats determines the age of onset and severity of symptoms.

3. Typical presentation

People ultimately diagnosed with SCA7 often present with numerous neurologic complaints, and gait disturbance is frequently the earliest sign. Patients may also mention a sway in the standing posture, a stagger while walking with a tendency to fall, and the adoption of a compensatory wide-base stance (ataxic gait). A lack of coordination of movement related to visual, spatial, and sensory information (dysmetria) is also commonly reported (e.g., an inability to judge step height and coordinate appropriate stepping response, resulting in difficulty climbing or descending stairs). Another common complaint is difficulty with repetitive pronation/supination movements (dysdiadochokinesia).

Later in the disease, patients will note difficulty with control of the tongue, throat, lips, and lungs (dysarthria/dysphagia), resulting in complaints related to respiration, phonation, resonance, prosody, swallowing, and articulation. These disorders are attributable to an interruption of afferent and efferent connections within the neocerebellar system.⁴

4. Reading lab results

The lab test is ordered as a SCA7 DNA test. Specimen type is whole blood. Test category is diagnostic (symptomatic). SCA7 is identified as CAG repeats 37->300 (normal range, 4-35) and a mutation on chromosome 3 in the ataxin-7 gene.⁴Figure 1 shows an example of a positive test result showing one allele (allele 1) in full mutation and one normal (allele 2).

5. After the diagnosis

Because there is no cure for SCA7, treatment is supportive only. Early diagnosis can help a patient alter his or her lifestyle to better adapt to progressive visual and muscular changes. Recommend routine physical exercise with light weight-bearing. Make sure the patient uses equipment that can be held onto (such as treadmills or elliptical trainers). Suggest using canes, walkers, grab bars, nonslip bath mats, ramps, and dressing hooks. Advise patients to remove all throw rugs from the residence, as these are slip-and-fall hazards. Remind them to use the elevator instead of the escalator. Before being hospitalized for surgery and diagnostic procedures, make sure all health-care providers (e.g. surgeons, anesthetists, internists, and nursing staff) are aware of the patient’s balance challenges so that assistive devices can be ordered for use during and after hospitalization. Instruct the patient on adjustments to be made whenever carrying objects—for example, not carrying cups more than two-thirds full of liquid. Finally, recommend the patient visit the National Ataxia Foundation Web site (www.ataxia.org) for more information on the condition.

6. Referral

A referral to a genetic counselor is advisable, as trinucleotide-repeat disorders like SCA7 typically increase in severity with each successive generation. For example, if an asymptomatic parent with 36 repeats produced a child with one more repeat (37), that child would be symptomatic. The anticipation of disease is higher in the offspring of affected males. These offspring usually acquire symptoms earlier, and the symptoms tend to be more severe in nature. All offspring are at a 50% risk of acquiring SCA7. When speaking or swallowing becomes an issue, refer to a speech therapist. Referral should also be made to a neuro-ophthalmologist and to a neurologist who specializes in movement disorders.