Clinical and laboratory diagnosis of spinocerebellar ataxia type 3 in a large Chinese family

Background: Hereditary ataxia is a group of hereditary diseases that are characterized by chronic progressive uncoordinated gait and are frequently associated with cerebellar atrophy.

Objectives: To investigate evidence-based diagnosis of hereditary ataxia by retrospective analysis of the diagnostic process in one Chinese family.

Methods: Clinical records of 15 ataxia patients from one Chinese family with 46 family members were retrospectively reviewed and a tentative diagnosis was made based on clinical manifestations, signs and symptoms, mode of inheritance, and progression. Since hereditary ataxia is a group of heterogeneous diseases having various subtypes and overlapping symptoms, we adopted a stepwise evaluation to achieve a tentative diagnosis. To confirm the diagnosis, we performed polymerase chain reaction (PCR) specific for the suspected causative gene of spinocerebellar ataxia (SCA) subtype 3 (SCA3).

Results: Through analysis of hereditary and clinical characteristics of family histories of the patients, we suspected that the family might suffer from SCA, especially, SCA3. The PCR assay for SCA3 showed that, five of the ten samples analyzed had a CAG trinucleotide expansion of the SCA3 gene, and four of the five members developed ataxia. The remaining one, a seven-year-old girl, showed no symptoms or signs except for uvula deviation. No clinical symptoms were found in five other members with negative PCR results. Thus, based on both clinical findings and laboratory results, we further confirmed that the family suffered from SCA3.

Conclusion: Hereditary ataxias are disorders sharing overlapping symptoms. Comprehensive analysis of medical and family records together with genetic diagnosis improves diagnostic efficiency of hereditary ataxia and aides in family counseling.