Clinical and genetic characteristics of type I sialidosis patients in mainland China

Abstract

Objective: Type I sialidosis (ST-1) is a rare autosomal recessive inherited disorder. To date, there has been no study on ST-1 patients in mainland China.

Methods: We reported in detail the cases of five Chinese ST-1 patients from two centers, and summarized all worldwide cases. Then, we compared the differences between Chinese and foreign patients.

Results: A total of 77 genetically confirmed ST-1 patients were identified: 12 from mainland China, 23 from Taiwan, 10 from other Asian regions, and 32 from European and American regions. The mean age of onset was 16.0 ± 6.7 years; the most common symptoms were myoclonus seizures (96.0%), followed by ataxia (94.3%), and blurred vision (67.2%). Compared to other groups, the onset age of patients from mainland China was much younger (10.8 ± 2.7 years). The incidence of visual impairment was lower in patients from other Asian regions than in patients from mainland China and Taiwan (28.6% vs. 81.8%-100%). Cherry-red spots were less frequent in the Taiwanese patients than in patients from other regions (27.3% vs. 55.2%-90.0%). Furthermore, 48 different mutation types were identified. Chinese mainland and Taiwanese patients were more likely to carry the c.544A > G mutation (75% and 100%, respectively) than the patients from other regions (only 0%-10.0%). Approximately 50% of Chinese mainland patients carried the c.239C > T mutation, a much higher proportion than that found in the other populations. In addition, although the brain MRI of most patients was normal, ¹⁸ F-FDG-PET analysis could reveal cerebellar and occipital lobe hypometabolism.

Interpretation: ST-1 patients in different regions are likely to have different mutation types; environmental factors may influence clinical manifestations. Larger studies enrolling more patients are required.

Figure 1

Examination results of patient 1. (A) Axial T1 brain magnetic resonance imaging was normal; (B) electroencephalogram showed bilateral polyspike and polyspike‐slow waves in the central, parietal, and midline regions; (C) fundus examination showed bilateral cherry‐red spots; (D) optical coherence tomography indicated bilateral diffuse weakness of the retinal nerve fiber layer and ganglion cell complex, as well as the hyperreflexivity of the macular inner layer; (E) somatosensory evoked potential showed a huge potential of bilateral N20‐P25 in the upper limb pathway.

Figure 2

Regions displaying hypometabolism in patient 1 compared with controls. ¹⁸F‐FDG‐PET analysis revealed hypometabolism of the left cuneus and lingual gyrus, right inferior semilunar lobule of the cerebellum, left cerebellar tonsil, and culmen of the cerebellum.

Figure 3

Mutation types of ST‐1 patients. (A–D) show the type and number of mutations in ST‐1 patients from the Chinese mainland, Taiwan, other Asian regions, and European and American regions, respectively. P means the number of patients; T means the mutation times. Each patient has two mutation sites (perhaps homozygosity) in the NEU1 gene, corresponding to two mutation “occurrences.” A mutation in the intron region of an Indian patient, g.2869A > T (1P, 1T), and a c.1258G > T (2P, 2T) mutation in the 3’‐UTR regions of two Americans patients are not marked in the figure.