A Turkish study has classified the genetic and observable characteristics of Friedreich’s ataxia (FA) and spinocerebellar ataxia (SCA) in patients diagnosed with hereditary cerebellar ataxia.
The study, “Determination of Genotypic and Phenotypic Characteristics of Friedreich’s Ataxia and Autosomal Dominant Spinocerebellar Ataxia Types 1, 2, 3, and 6”, appeared in the journal Archives of Neuropsychiatry.
Ataxias may be classified as congenital, hereditary, non-hereditary and symptomatic. Hereditary ataxias may be autosomal-dominant, which means that inheriting the abnormal gene from one parent is enough to develop the disease. Conversely, ataxias may also be autosomal-recessive, meaning that a child has a 25 percent probability of inheriting the disease from heterozygous parents who only carry a copy of the defective gene.
Clinical diversity within subtypes of SCA — an autosomal-dominant ataxia — makes it critical to study its genetic causes in order to properly classify the disease. Bases on genetic analysis, SCA types 1, 2, 3 and 6 (which are distinguished by a specific gene mutation and show different symptom development) are among the most common worldwide.
These subtypes feature an accumulation of polyglutamine products inside the cells that lead to neuron damage. SCA prevalence has been reported at 3 out of 100,000 inhabitants in certain geographical regions.
FA, the most common autosomal recessive ataxia, represents 75 percent of all ataxias starting before the age of 25 years. FA prevalence varies between 1 in 20,000 and 1 in 125,000 individuals. In FA, respiratory activity in mitochondria — the cellular organelle responsible for energy production — declines and toxic free radicals accumulate in the cell.
Halil Kasap, of Turkey’s Çukurova University Faculty of Medicine in Adana, led a research team that analyzed cases of hereditary ataxia to investigate the occurrence of FA and SCA types 1, 2, 3, and 6. Their study included 144, of which 129 were diagnosed with hereditary cerebellar ataxia through clinical and laboratory findings, and 15 were sibling patients diagnosed through family scans.
The team performed detailed physical and neurological examinations, including electrophysiological, imaging and cardiac analyses, for all cases. Researchers also collected blood samples were collected and isolated DNA to perform genetic analyses.
Lack of balance was the main and first complaint in all group, though scientists also widely observed weakness. Less common were mental retardation (14.7 percent of cases) and optical atrophy (16.1 percent) — both of which were absent in SCA types 1 and 6.
Researchers found skeletal deformities in all groups, with some varieties exclusively among FA patients. They observed electrophysiological abnormalities and spinal cord atrophy in FA only, though they did detect significant differences in cerebellar atrophy in FA and SCA6. They also detected abnormal cardiac findings in four FA cases.
In terms of frequency, 47 percent of the cases were FA. Disease onset was about 12 years, which matches the literature. Moreover, they detected two SCA1 cases and one SCA6 case. Clinical findings in SCA1 started at around age 40.
“Patients with cerebellar ataxia of hereditary origin should be primarily examined for FA,” the study said, adding that if FA can be ruled out, clinicians should consider SCA and other causes of ataxia.