PP1103 - Illuminating the Hidden: A Case-Based Review of Hearing Loss in Hunter Syndrome (MPS II)

Abstract:
Hunter syndrome (Mucopolysaccharidosis II) is a rare X-linked recessive genetic disorder primarily affecting males. This condition arises from a mutation in the IDS gene on the X chromosome, which is responsible for producing the iduronate 2-sulfatase (IDS) enzyme. This enzyme mutation in Hunter syndrome causes buildup of complex sugars in various tissues. The signs and symptoms, including audiologic manifestations, of Hunter syndrome in a 20-year-old male will be presented. The diagnostic approaches and management strategies specific to hearing loss will be addressed. The essential role of audiologists as part of the multidisciplinary care team will be highlighted.

Summary:
Hunter syndrome or mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive genetic disorder commonly caused by deletion, insertion, or point mutations of the IDS gene on chromosome Xq28. It's a lysosomal storage disease caused by deficient iduronate 2-sulfatase enzyme needed to break down complex sugar molecules, glycosaminoglycans (GAGs), which accumulate in cells resulting in multi-systemic progressive damage. Each male offspring of carrier mothers has a 50% chance of inheriting this condition while each female offspring has a 50% chance of being a carrier. There is no father-to-son transmission.

There are two types of Hunter’s syndrome, mild and severe (early-onset). The severe type shows progressive intellectual disability and a shorter life span (10-20 years). Children may have no symptoms at birth but can begin to appear between 18 months and four-years. Signs and symptoms can include: (a) facial dysmorphism and large head, (b) enlarged organs with abdominal distension and hernia, (c) upper respiratory tract infections and otitis media, (d) cardiac problems, and (c) behavioral symptoms including aggressive behavior and impaired cognitive function (Children’s Hospital, Philadelphia, n. d).

Hearing loss is commonly reported with prevalence rates between 67.3% to 94% (Wolfberg et al., 2020). The hearing loss is initially conductive but can progress to a mixed or sensorineural hearing loss (SNHL), ranging in severity from mild to profound (Wolfberg et al., 2020). Conductive hearing loss is attributed to accumulation of GAGs in the middle ear/eustachian tube causing tympanic membrane thickening and ossicular chain abnormalities (Rao et al., 2024). Etiology for SNHL is not well understood but may involve GAG deposits in inner ear structures/auditory nerve pathway (Wolfberg, 2020). Communication skills can deteriorate due to progressive language deficits and hearing loss. (Rao et al., 2024).

Zephyr, a 20-year-old male was seen for a comprehensive audiologic evaluation and hearing aid consult. He was diagnosed with MPS II at birth and had a documented hearing loss for 10 years. Zephyr had used amplification in the past but had lost the hearing aids and was unaided for the past 4-5 years. Audiologic evaluation of patients with Hunter syndrome requires a comprehensive and tailored approach, which may include physiologic test measures as these children can be difficult-to-test behaviorally. Zephyr probably had a milder form of Hunter’s; he provided reliable behavioral response with minimal test instructions. Test results showed normal tympanograms and a fairly symmetrical moderate to moderately severe SNHL with a conductive component at 500 Hz bilaterally. Word recognition scores were excellent bilaterally. Zephyr actively participated in the RIC hearing aid selection process.

Hearing loss is prevalent in MPS II, although frequently under-diagnosed and can negatively impact quality of life. Amplification plays a crucial role in patient management especially given that the hearing loss can be progressive. The critical role of audiologists in a multidisciplinary team will be discussed. Enzyme replacement therapy (ERT) has shown some promise in stabilizing hearing function by improving the conductive component. Impact of ERT on SNHL remains unclear. Gene therapy trials for MPS II are also underway (Franchi et al, 2023).

Learning Objectives:

• Upon completion, participants will be able to discuss the genetic basis of Hunter syndrome and its audiologic manifestations.
• Upon completion, participants will be able to develop appropriate audiologic management strategies for Hunter syndrome as part of a multidisciplinary team.