Mucopolysaccharidosis IVB and sensorineural deafness associated with the CDH23 gene: A unique clinical case

Abstract

BACKROUND: Mucopolysaccharidoses are a group of lysosomal storage diseases belonging to orphan diseases. Certain types of mucopolysaccharides have a typical musculoskeletal findings and radiological changes. The mucopolysaccharidosis IVB is a rare type. Thus, 95% of cases of the mucopolysaccharidosis IV are subtype A. CLINICAL CASE: Сlinical and radiological changes and genetic examination were performed to a 9-year-old patient with sensorineural deafness who applied to a medical institution with complaints of right hip pain and limping. DISCUSSION: Based on complaints and radiological changes of the hip joints, the patient was initially diagnosed with LeggCalvePerthes disease. The presence of a symmetrical bilateral process, pathognomonic changes in the acetabulum and femoral heads, and an atypical clinic of LeggCalvePerthes disease made us suspect mucopolysaccharidos. Enzymatic analysis revealed a significant decrease in the beta-D-galactosidase enzyme activity. In addition, two compound heterozygous variants in the GLB1 gene were identified: the pathogenic variant c.808TG, inherited from the father, and an insertion of a mobile genetic element, inherited from the mother. Only one variant in the GLB1 gene was detected in the brother (born in 2009), and none of the above GLB1 variants was detected in the older brother (born in 2003). Moreover, the proband (with clinical mucopolysaccharidos IVB) and his brother (born in 2009) (without mucopolysaccharidos IVB) inherited pathogenic CDH23 variants (c.6992TC and c.805CT) from their mother and father, respectively, which is consistent with their having sensorineural hearing loss. CONCLUSIONS: The uniqueness of this clinical case is the presence of the rare type of mucopolysaccharidos and the separate genetic cause of sensorineural hearing loss in a single patient. The diagnosis of mucopolysaccharidos IVB in the proband was confirmed by biochemical and molecular genetic tests, and the diagnosis of CDH23-associated sensorineural deafness in the proband and brother (born in 2009) was confirmed by molecular genetic testing.