Clinical phenotype and GNPTAB gene mutation spectrum analysis of Chinese patients with mucolipidosis type II α/β.

Background: Mucolipidosis type II α/β (ML II α/β) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the Methods: Whole-exome sequencing (WES) was performed on a new proband, and a comprehensive literature review was conducted, summarizing a total of 56 Chinese cases (including 1 new case). Results: All patients presented with skeletal deformities (100%), 96.4% had coarse facial features, 94.6% had developmental delay, and the median age at diagnosis was 17.5 months. The new proband carried compound heterozygous non-sense mutations NM_024312.4:c.2455G>T (p.Glu819*) and NM_024312.4:c.1123C>T (p.Arg375*) and died of respiratory failure at 27 months of age. Notably, NM_024312.4:c.1090C>T (p.Arg364*) was the most common mutation (found in 39.3% of patients), associated with typical skeletal abnormalities and early death. Cardiac abnormalities (16.1%) and pulmonary complications (12.5%) were common comorbidities. Conclusion: This study identified a unique mutational hotspot in Chinese patients with ML II α/β and revealed a severe phenotype with poor prognosis, primarily resulting in death from respiratory failure. These findings are beneficial for clinical diagnosis, genetic counseling, and targeted molecular screening of this disease.