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One Family's Search to Explain a Fatal Neurological Disorder

With their help, researchers are advancing the 70-year effort to understand—and treat—hereditary ataxia.

Nissa Mollema, Harry Orr

An Unwanted Family Inheritance

2013-11MollemaF2.jpgClick to Enlarge ImageOnce diagnosed, family members researched what ataxia was. Ataxia is derived from the Greek term for "lack of order," and means having little control over muscle movements. Patients with ataxia walk with a wide stance and shuffling, small steps in an attempt to maintain balance. Their fine motor skills are also lost: They struggle to bring an outstretched finger to touch their noses. Henry's father lost the ability to tie his shoes, dress himself, and feed himself as the disease progressed. Ataxia robbed him of his ability to control both his fine and gross muscle movements, making each motion challenging and inefficient.

A variety of causes can result in ataxic symptoms. People who have had too much alcohol display temporary ataxia—they stagger and have difficulty keeping their balance. Permanent forms of ataxia, in contrast, can be debilitating and sometimes deadly. A traumatic brain injury, such as stroke or head trauma, may trigger ataxia. As the patient recovers from the injury, the ataxia may improve. More complex forms of permanent ataxia are caused by genetic mutations. In these cases, mutations that cause the disorder are passed from parent to child. Sporadic cases of ataxia, in which a patient with no family history of the disorder is diagnosed with the disease, are more mysterious. Hereditary and sporadic ataxias currently affect roughly 150,000 people in the United States and are typically progressive in nature, making the individual more disabled as the disease advances.

The doctors at the University of Minnesota took a particular interest in the ataxia that ran in Henry's family during Bert's visit to the hospital. At the time, the only form of hereditary ataxia that was known was Friedreich's ataxia, which was described in 1863. The pattern of inheritance seen in Henry's family was different from that seen in Friedreich's ataxia. Unlike Friedreich's ataxia, the ataxia in Henry's family affected members in each generation, instead of skipping generations.

Family members with ataxia also presented with a variety of symptoms that differed from Friedreich's ataxia, suggesting that they had a form of ataxia that had never been diagnosed. In this new ataxic disorder, slow, progressive symptom onset began between the ages of 20 and 30. Patients usually noticed problems with their lower limbs first and began having difficulty keeping their balance while walking. The university doctors suspected that the symptoms of ataxia were the result of degeneration in the brain or spinal cord.

2013-11MollemaF3.jpgClick to Enlarge ImageTo better understand the genetic nature of the disease, the doctors asked Henry to create a family tree documenting which individuals were affected or unaffected by the disorder. The Schuts' family tree supported the fact that only family members with ataxia could pass the disorder to their children and that the disease displayed a dominant mode of inheritance (50 percent of children were affected).

Although the family now had a diagnosis for the disease and a better understanding of how it was inherited, no one had information about the cause of the disease or how to treat it. Clinicians advised the affected family members to eat well and exercise, yet this did little to prevent progression of the disorder. For 10 years, Bert continued to become more disabled, until he passed away from ataxia in 1939 at the age of 30. At the encouragement of physicians, Bert's brain was sent to University of Minnesota to be studied. As doctors had previously predicted, extensive degeneration was seen within the spinal cord, which controls involuntary functions, and within the cerebellum, which controls voluntary movement. Physicians named the disease spinocerebellar ataxia type 1 (SCA1) because of the regions involved. But they still had no treatment or explanation for why it was occurring.

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