To systematically describe the clinical spectrum and mutational characteristics of Chinese patients with Mucolipidosis type II α/β (ML II α/β) to facilitate early diagnosis and provide ethnicity-specific data.
Approach:
Clinical Data Collection: Detailed clinical data were collected from newly diagnosed ML II α/β patients, including clinical manifestations, physical examinations, and various laboratory tests.
Genetic Testing: Whole-exome sequencing (WES) was performed on a new proband and the patient's parents to identify mutations.
Literature Review: A comprehensive literature review was conducted, summarizing a total of 56 Chinese cases of ML II α/β.
Key Findings:
All patients presented with skeletal deformities (100%).
96.4% had coarse facial features and 94.6% had developmental delay.
The median age at diagnosis was 17.5 months.
The most common mutation was NM_024312.4:c.1090C>T (p.Arg364*), found in 39.3% of patients.
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*).
Common comorbidities included cardiac abnormalities (16.1%) and pulmonary complications (12.5%).
Interpretation:
The 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.
Limitations:
The study is limited to a specific ethnic group, which may not represent the global population.
The sample size, while comprehensive, may still be insufficient to capture all genetic variability in ML II α/β.
Conclusion:
These findings are beneficial for clinical diagnosis, genetic counseling, and targeted molecular screening of ML II α/β.
