A 16-year-old male patient visited our ophthalmology department due to deteriorating vision in both eyes over the past year. His parents were not related to one another, he was delivered by cesarean section after 38 weeks and weighed 2600 g at birth, and his parents and sister presented with normal vision and stature. His parents said the patient was normal at birth, but developed skeletal abnormalities at age one. When he was 9 years old, the patient visited the Beijing Children’s Hospital, but there was no definitive diagnosis. Slit-lamp examination of both eyes demonstrated corneal haze, and a Goldmann applanation tonometer showed that his intraocular pressure was 26.7 mmHg and 17.3 mmHg in his right and left eye, respectively. Uncorrected visual acuity was 0.25 in his right eye and 0.5 in his left eye. Of note, his best-corrected visual acuity did not increase: right eye + 4.5 DS/− 1.5 DC = 0.25, left eye + 3.5 DS/− 2.0 DC = 0.5. The axial length measured using an ultrasonic pachymeter showed the right eye to be 20.39 mm and the left eye to be 20.27 mm. Endothelial cell counts could not be determined due to the corneal opacity of the patient. Although the patient exhibited normal intelligence, physical examination revealed kyphotic deformities, short stature (compared to peers), skeletal and joint deformity, sternum herniation, thick lips, long fingers, coarse facial features, and a flat nasal bridge. Taken together, we could not provide a definite diagnosis according to the ocular manifestations with systemic manifestations, but we suspected that he had a rare hereditary syndrome. Therefore, we recommend the consanguineous family to make genetic diagnosis. All subjects provided signed informed consent, this study was approved by the Ethics Committee of the Affiliated Hospital of Yunnan University and was performed in accordance with the Declaration of Helsinki. Peripheral venous blood samples (5 ml) were drawn from the patient and his parents for genetic testing. Genetic assessments revealed two heterozygous missense mutations in the ARSB gene, exon 7 c.1325G > A (p.Thr442Met) (M1) and exon 6 c.1197G > C (p.Phe399Leu) (M2), co-segregated with the disease phenotype in this family, and his healthy parents were heterozygous carriers (father: c.1197G > C, mother: c.1325G > A). The mutated areas were found in a highly conserved segment of the ARSB protein in humans and other species, and affected amino acids 399 (phenylalanine) and 442 (threonine). According to the American College of Medical Genetics and Genomics, and analysis of four bioinformatics platforms (SIFT, Mutation Taster, Polyphen2, and REVEL), M1 was proposed as a pathogenic mutation and M2 was classified as likely pathogenic []. The global MAF of p.Phe399Leu was low [MAF(gnomAD) = 0.003]; however, the global MAF of p.Thr442Met was not found in the databases. Structural modeling of the ARSB protein demonstrated that both Phe399 and Thr442 were located in the first β-sheet, which was required for receptor binding. The mutation caused the hydrogen bond between the amino acids to break, which resulted in protein structural instability. The patient was confirmed to have MPS VI because of the compound heterozygous mutations of ARSB.