Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics

Abstract Introduction: Maternally inherited diabetes and deafness (MIDD) is a multisystem disorder characterized by insulinopenia and sensorineural hearing loss. This rare form of monogenic diabetes is most commonly associated with the A3243G mutation of mitochondrial DNA (mtDNA). The same mutation is seen in 80 percent of patients with MELAS (Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). MIDD and MELAS have overlapping features suggesting a continuum of expression for the A3243G mutation. Clinical Case: A 41-year-old male was referred for genetic testing and counseling by his ophthalmologist following detection of bilateral punched-out retinal pigment epithelium (RPE) lesions on routine exam. His medical history was significant for type 1 diabetes mellitus (T1DM) diagnosed at the age of 21 and bilateral sensorineural hearing loss diagnosed at the age of 38. The referral was triggered by patient reported family history of MELAS in two of his brothers who were both diagnosed at the age of 10 and died at the ages of 20 and 27. Whether the patient was previously tested during early childhood remains unclear. His medical history was negative for stroke-like episodes or seizures. Neurologic evaluation revealed mild fluent aphasia with paraphasic errors and some comprehension difficulties. MRI of the brain without contrast showed no focus of restricted diffusion. Mitochondrial DNA sequence analysis was performed. A pathogenic variant (m.3243 A>G) was detected in the MT-TL1 gene at approximately 25% heteroplasmy. The patient was advised to avoid metformin given increased risk for lactic acidosis. He was also instructed against use of statins. At the age of 45, the patient presented to the emergency department (ED) with a complaint of headache, vertigo and incoordination. Physical examination revealed left homonymous hemianopsia, right horizontal nystagmus and bilateral upper extremity dysmetria. MRI of the brain without contrast showed a large area of predominantly cortical restricted diffusion involving the right temporal and occipital region with associated T2/FLAIR hyper-intensity. Cross over between the PCA and MCA territories was suggestive of a stroke-like episode related to MELAS. The patient received a bolus of IV arginine at 0.5 g/kg followed by an IV infusion of 0.5 g/kg/day for 3 days. He was later transitioned to oral arginine 5g three times daily and was discharged to a rehab facility. Clinical Lesson: This case demonstrates the evolution of MIDD to MELAS, supporting the concept that both syndromes represent a spectrum of the same disease. A few case reports describe the progression of MIDD to MELAS. Why some patients develop MELAS and others develop MIDD is unclear but may be related to heteroplasmy. Early identification of MIDD and MELAS is crucial given associated comorbidities and unique management issues.

Download Full-text

Mitochondrial DNA A3243G mutation in noise-induced sensorineural hearing loss

Korean Journal of Occupational and Environmental Medicine ◽

10.35371/kjoem.2000.12.3.319 ◽

2000 ◽

Vol 12 (3) ◽

pp. 319

Author(s):

Dong Hoon Shin ◽

Won Ki Baek ◽

In Sung Chung

Keyword(s):

Hearing Loss ◽

Mitochondrial Dna ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

A3243g Mutation

Download Full-text

Sudden sensorineural hearing loss in patients with vestibular schwannoma

Scientific Reports ◽

10.1038/s41598-020-80366-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Koichiro Wasano ◽

Naoki Oishi ◽

Masaru Noguchi ◽

Ko Hentona ◽

Seiichi Shinden ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Clinical Features ◽

Vestibular Schwannoma ◽

Recovery Rate ◽

Treatment Plan ◽

Full Range ◽

Sudden Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Recurrence Time

AbstractClinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.

Download Full-text