Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

Wolfberg, Jeremy; Chintalapati, Keerthana; Tomatsu, Shunji; Nagao, Kyoko

doi:10.3390/diagnostics10080554

Cited by 12 publications

(10 citation statements)

References 112 publications

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“…ARSB gene variants have often been associated to the lysosomal storage disorder MPS VI (30). Conductive hearing loss has been linked to MPS VI and other MPS subtypes (31). ARSB enzyme levels in the patient's DBS were measured twice, and the results supported the MPS VI diagnosis.…”

Section: Discussionmentioning

confidence: 65%

Case Report: Reinterpretation and Reclassification of ARSB:p.Arg159Cys Variant Identified in an Emirati Patient With Hearing Loss Caused by a Pathogenic Variant in the CDH23 Gene

et al. 2022

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Arylsulfatase B is an enzyme present in the lysosomes that involves in the breakdown of large sugar molecules known as glycosaminoglycans (GAGs). Arylsulfatase B chemically modifies two GAGs, namely, dermatan sulfate and chondroitin sulfate, by removing the sulfate group. Mutations in the gene encoding the arylsulfataseB enzyme causes lysosomal storage disorder, mucopolysaccharidosis type VI (MPS VI), or Maroteaux–Lamy syndrome. In this study, we report a case of congenital hearing loss with mild pigmentary changes in the retina, indicative of Usher syndrome, and a missense variant reported as likely pathogenic for MPS VI. Sequencing results identified a pathogenic missense variant p.Arg1746Gln in the CDH23 gene. However, another missense variant ARSB:p.Arg159Cys was reported as likely pathogenic to the treating physician. Mutations in ARSB gene have been associated with MPS VI. Subsequently, ARSB enzyme activity was found low twice in dried blood spot (DBS), suggestive of MPS VI. The patient did not have the clinical features of MPS VI, but considering the wide clinical spectrum, progressive nature of MPS VI, and the fact that a treatment for MPS VI is available to prevent disease progression, further biochemical, enzymatic, and in silico studies were performed to confirm the pathogenicity of this variant. In silico tools predicted this variant to be pathogenic. However, the results of urine and serum GAGs and ARSB enzyme levels measured from patient's fibroblast were found normal. Based on clinical and biochemical findings, ARSB:p.Arg159Cys is likely benign and did not support the diagnosis of MPS VI. However, CDH23:p.Arg1746Gln, a pathogenic variant, supports the underlying cause of hearing loss. This study highlights the importance of a robust correlation between genetic results and clinical presentation, and biochemical and enzymatic studies, to achieve a differential diagnosis.

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Section: Discussionmentioning

confidence: 65%

Case Report: Reinterpretation and Reclassification of ARSB:p.Arg159Cys Variant Identified in an Emirati Patient With Hearing Loss Caused by a Pathogenic Variant in the CDH23 Gene

et al. 2022

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“…Systemic administration of ETV:IDS corrects auricular and skeletal phenotypes. Progressive conductive and sensorineural hearing losses, resulting from GAG accumulation in the middle ear and recurrent otitis, are common in patients with MPS II (30,31). Although there are limited clinical data on the efficacy of ERT on auditory function, data support an improvement in hearing and reduction of GAGs in the outer and middle ear of MPS II mice in response to peripherally administered ERT (28).…”

Section: Resultsmentioning

confidence: 99%

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome

Arguello¹,

Meisner²,

Thomsen³

et al. 2021

JCI Insight

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“…Non-ocular clinical manifestations of MPSs were also obstacles to diagnosis of glaucoma. Clinical manifestations of MPSs that blocked communication, including hearing loss and mental-retardation, may hinder doctors from understanding the condition of patients with MPSs [2,48]. MPSs patients with bone diseases may have difficulty in posing for evaluation/imaging [49].…”

Section: Diagnosis Of Glaucoma In Mpssmentioning

confidence: 99%

“…MPSs are classified into seven subtypes. Six subtypes of MPSs (type I, III, IV, VI, VII and IX) are inherited in an autosomal recessive manner, while mucopolysaccharidosis (MPS) II is X-linked [2]. Milder forms of MPS I and II, MPS IV, and MPS VI are not considered to be progressive or neuronopathic, although patients may function abnormally in neurocognitive ability and/or behavior [3].…”

Section: Introductionmentioning

confidence: 99%

Glaucoma in mucopolysaccharidoses

Kong

Zhang

Cheng³

et al. 2021

Orphanet J Rare Dis

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Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low prevalence and high childhood mortality, researches on mucopolysaccharidoses were mainly focused on the fatal manifestations. With the development of treatments, more and more mucopolysaccharidoses patients were treated by approved therapies, thereby getting prolonged life span and improved quality of life. Abnormal accumulation of glycosaminoglycans in the eye may block trabecular meshwork, thicken sclera and change mechanical behavior of lamina cribrosa, which, by increasing intraocular pressure and damaging optic nerve, could cause glaucoma. Glaucoma was the leading cause of irreversible blindness worldwide, but it was rarely reported in mucopolysaccharidoses patients. Although non-fatal, it seriously affected quality of life. Prevalence of glaucoma in mucopolysaccharidoses patients (ranged from 2.1 to 12.5%) indicated that glaucoma in patients with mucopolysaccharidoses was worthy of attention and further study, thereby improving the quality of life for MPSs patients.

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Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

Cited by 12 publications

References 112 publications

Case Report: Reinterpretation and Reclassification of ARSB:p.Arg159Cys Variant Identified in an Emirati Patient With Hearing Loss Caused by a Pathogenic Variant in the CDH23 Gene

Case Report: Reinterpretation and Reclassification of ARSB:p.Arg159Cys Variant Identified in an Emirati Patient With Hearing Loss Caused by a Pathogenic Variant in the CDH23 Gene

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome

Glaucoma in mucopolysaccharidoses

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